JP4728340B2 - Compounds that modulate thrombopoietin activity and methods of modulation - Google Patents

Description

  The present invention relates to compounds that modulate one or more thrombopoietin activities and / or bind to thrombopoietin receptors; and methods of making and using the compounds.

  Thrombopoietin (TPO), which is also called c-MPl ligand, mpl ligand, megapoietin, and megakaryocyte proliferation, and development factor, is a glycoprotein known to be involved in platelet production. For example, Wendling, F. et al., Biotherapy 10 (4): 269-77 (1998); Kuter DJ et al., The Oncologist, 1: 98-106 (1996); and Metcalf ( Metcalf), Nature 369: 519-520 (1994). TPO has been cloned and its amino acid sequence and the cDNA sequence encoding it have been described. See, for example, US Pat. No. 5,766,581; Kuter, DJ et al., Proc. Natl. Acad. Sci., 91: 11104-11108 (1994); de Sauvage FV et al., Nature, 369: 533. -538 (1994); by Lok, S. et al., Nature 369: 565-568 (1994); and by Wending, F. et al., Nature, 369: 571-574 (1994).

  In certain instances, TPO activity results from binding of TPO to a TPO receptor (also referred to as MPL). The TPO receptor has been cloned and its amino acid sequence has been described. See, for example, Vigon et al., Proc. Natl. Acad. Sci., 89: 5640-5644 (1992).

  In certain instances, TPO modulators can be useful for treating a variety of hematopoietic diseases, including but not limited to thrombocytopenia. See, for example, Baser et al., Blood 89: 3118-3128 (1997); Fanucchi et al., New Engl. J. Med. 336: 404-409 (1997). For example, chemotherapy (eg, including but not limited to chemotherapy and / or radiation therapy for the treatment of cancer) can reduce platelet levels. In certain instances, treatment of a patient with a selective TPO modulator increases platelet levels. In certain instances, selective TPO modulators can stimulate glial cell production, thereby resulting in repair of damaged neurons.

  TPO mimetics have been previously described. See, for example, WO 03 / 103686A1; and WO 01/21180.

［式中、
Ｒ^１は、ＣＯ_２Ｒ^１０、ＣＯＮＲ^１０Ｒ^１１、ＳＯ_３Ｒ^１０、またはカルボン酸生物学的等価体から選ばれ；
Ｒ^２およびＲ^３は各々独立して、なし、水素、ＯＲ^１２、ＮＲ^１２Ｒ^１３、場合により置換されたＣ_１〜Ｃ_４脂肪族、場合により置換されたＣ_１〜Ｃ_４ハロ脂肪族、場合により置換されたＣ_１〜Ｃ_４ヘテロ脂肪族、場合により置換された環、または(ＣＨ_２)_ｍＲ^１４から選ばれるか；あるいは、Ｒ^２およびＲ^３は一緒になって場合により置換されたオレフィンを形成するか；あるいは、Ｒ^２およびＲ^３は連結して場合により置換されたＣ_３〜Ｃ_８環を形成し；
Ｒ^４は、水素、Ｆ、Ｃｌ、Ｂｒ、Ｃ_１〜Ｃ_４脂肪族、Ｃ_１〜Ｃ_４ハロ脂肪族、Ｃ_１〜Ｃ_４ヘテロ脂肪族、または環から選ばれ；
Ｒ^５は、水素、ＯＲ^１０、ＳＲ^１０、ＮＨＲ^１１、またはＣＯ_２Ｈから選ばれ；
Ｒ^６は、水素、ＯＲ^１２、ＮＲ^１２Ｒ^１３、Ｆ、Ｃｌ、Ｂｒ、Ｃ_１〜Ｃ_４アルキル、Ｃ_１〜Ｃ_４ハロアルキル、Ｃ_１〜Ｃ_４ヘテロアルキル、または環から選ばれ；
Ｒ^７は、水素、場合により置換されたＣ_１〜Ｃ_８脂肪族、場合により置換されたＣ_１〜Ｃ_８ハロ脂肪族、場合により置換されたＣ_１〜Ｃ_８ヘテロ脂肪族、場合により置換されたＣ_１〜Ｃ_８ヘテロハロ脂肪族、場合により置換された環、または(ＣＨ_２)_ｍＲ^１４から選ばれ；
Ｒ^１０は、水素、場合により置換されたＣ_１〜Ｃ_４脂肪族、Ｃ_１〜Ｃ_４ハロ脂肪族、Ｃ_１〜Ｃ_４ヘテロ脂肪族、または環から選ばれ；
Ｒ^１１は、水素、ＳＯ_２Ｒ^１５、Ｃ_１〜Ｃ_４脂肪族、Ｃ_１〜Ｃ_４ハロ脂肪族、Ｃ_１〜Ｃ_４ヘテロ脂肪族、または環から選ばれ；
Ｒ^１２およびＲ^１３は各々独立して、水素、場合により置換されたＣ_１〜Ｃ_４脂肪族、場合により置換されたＣ_１〜Ｃ_４ハロ脂肪族、場合により置換されたＣ_１〜Ｃ_４ヘテロ脂肪族、場合により置換された環、または(ＣＨ_２)_ｍＲ^１４から選ばれるか；あるいは、Ｒ^１２およびＲ^１３の一方は場合により置換されたＣ_２〜Ｃ_６脂肪族または場合により置換された環であって、そしてＲ^１２およびＲ^１３の他方はなしであるか；あるいは、Ｒ^１２およびＲ^１３は連結して場合により置換されたＣ_３〜Ｃ_８環を形成し；
Ｒ^１４は、場合により置換されたアリールまたは場合により置換されたヘテロアリールから選ばれ；
Ｒ^１５は、水素、Ｃ_１〜Ｃ_３脂肪族、Ｃ_１〜Ｃ_３ハロ脂肪族、または環から選ばれ；
Ｙは、場合により置換されたＣ_１〜Ｃ_６脂肪族、場合により置換されたＣ_１〜Ｃ_６ヘテロ脂肪族、場合により置換されたフェニル、場合により置換されたヘテロアリール、場合により置換されたＣ_３〜Ｃ_５ヘテロ環、または場合により置換された脂環式から選ばれる１個以上の基を含有する１〜４の原子数のスペーサーであり、但し、Ｙは、ジヒドロピラゾールを形成するように配向した−Ｎ＝ＣＲ^６−ではなく；
Ｚは、
場合により置換されたＣ_６〜Ｃ_１０アリールもしくは場合により置換されたＣ_１〜Ｃ_８ヘテロアリールから選ばれる、２〜５の原子数のスペーサー、または、
場合により置換されたＣ_１〜Ｃ_６脂肪族、場合により置換されたＣ_１〜Ｃ_６ヘテロ脂肪族、もしくは場合により置換されたＣ_１〜Ｃ_６ハロ脂肪族から選ばれる、１〜５の原子数のスペーサー、
から選ばれ；
ｍは、０、１、または２であり；そして、
ｎは、０または１である］
で示される化合物、またはその医薬的に許容し得る塩、エステル、アミド、もしくはプロドラッグを提供する。 (Summary of Invention)
In certain embodiments, the present invention provides compounds of formula (I):

[Where:
R ¹ is selected from CO ₂ R ¹⁰ , CONR ¹⁰ R ¹¹ , SO ₃ R ¹⁰ , or a carboxylic acid biological equivalent;
R ² and R ³ are each independently none, hydrogen, OR ¹² , NR ¹² R ¹³ , optionally substituted C ₁ -C ₄ aliphatic, optionally substituted C ₁ -C ₄ haloaliphatic, Selected from optionally substituted C ₁ -C ₄ heteroaliphatic, optionally substituted ring, or (CH ₂ ) _m R ¹⁴ ; alternatively, R ² and R ^{3 taken} together are optionally substituted Or R ² and R ³ are joined to form an optionally substituted C ₃ -C ₈ ring;
R ⁴ is selected from hydrogen, F, Cl, Br, C ₁ -C ₄ aliphatic, C ₁ -C ₄ haloaliphatic, C ₁ -C ₄ heteroaliphatic, or a ring;
R ⁵ is selected from hydrogen, OR ¹⁰ , SR ¹⁰ , NHR ¹¹ , or CO ₂ H;
R ⁶ is selected from hydrogen, OR ¹² , NR ¹² R ¹³ , F, Cl, Br, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl, or a ring;
R ⁷ is hydrogen, optionally substituted C ₁ -C ₈ aliphatic, optionally substituted C ₁ -C ₈ haloaliphatic, optionally substituted C ₁ -C ₈ heteroaliphatic, optionally substituted Selected from C ₁ -C ₈ heterohaloaliphatic, optionally substituted rings, or (CH ₂ ) _m R ¹⁴ ;
R ¹⁰ is selected from hydrogen, optionally substituted C ₁ -C ₄ aliphatic, C ₁ -C ₄ haloaliphatic, C ₁ -C ₄ heteroaliphatic, or a ring;
R ¹¹ is selected from hydrogen, SO ₂ R ¹⁵ , C ₁ -C ₄ aliphatic, C ₁ -C ₄ haloaliphatic, C ₁ -C ₄ heteroaliphatic, or a ring;
R ¹² and R ¹³ are each independently hydrogen, optionally substituted C ₁ -C ₄ aliphatic, optionally substituted C ₁ -C ₄ haloaliphatic, optionally substituted C ₁ -C ₄ Selected from heteroaliphatic, optionally substituted ring, or (CH ₂ ) _m R ¹⁴ ; alternatively, one of R ¹² and R ¹³ is optionally substituted C ₂ -C ₆ aliphatic or optionally substituted And the other of R ¹² and R ¹³ is none; alternatively, R ¹² and R ¹³ are linked to form an optionally substituted C ₃ -C ₈ ring;
R ¹⁴ is selected from optionally substituted aryl or optionally substituted heteroaryl;
R ¹⁵ is selected from hydrogen, C ₁ -C ₃ aliphatic, C ₁ -C ₃ haloaliphatic, or a ring;
Y is optionally substituted C ₁ -C ₆ aliphatic, optionally substituted C ₁ -C ₆ heteroaliphatic, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted A spacer of 1 to 4 atoms containing one or more groups selected from C _{3 to} C ₅ heterocycles or optionally substituted alicyclics, provided that Y forms a dihydropyrazole. instead - -N = CR ⁶ oriented in;
Z is
Optionally selected from _C 1 -C ₈ heteroaryl, which are optionally substituted by a _C 6 _{-C 10} aryl or substituted, the number of 2 to 5 atom spacer, or,
1 to 5 atoms selected from optionally substituted C ₁ -C ₆ aliphatic, optionally substituted C ₁ -C ₆ heteroaliphatic, or optionally substituted C ₁ -C ₆ haloaliphatic Number of spacers,
Chosen from;
m is 0, 1, or 2; and
n is 0 or 1]
Or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof.

（式中、Ａ、ＢおよびＣは各々独立して、Ｏ、ＳまたはＮから選ばれる）
から選ばれるカルボン酸生物学的等価体から選ばれ；
Ｒ^２およびＲ^３は各々独立して、水素、ＯＲ^１２、ＮＲ^１２Ｒ^１３、場合により置換されたＣ_１〜Ｃ_４アルキル、場合により置換されたＣ_１〜Ｃ_４ハロアルキル、場合により置換されたＣ_１〜Ｃ_４ヘテロアルキル、場合により置換された環、または(ＣＨ_２)_ｍＲ^１４から選ばれるか；あるいは、Ｒ^２およびＲ^３は一緒になって場合により置換されたオレフィンを形成するか；あるいは、Ｒ^２およびＲ^３は連結して場合により置換されたＣ_３〜Ｃ_８環を形成し；
Ｒ^４は、水素、Ｆ、Ｃｌ、Ｂｒ、Ｃ_１〜Ｃ_４アルキル、Ｃ_１〜Ｃ_４ハロアルキル、Ｃ_１〜Ｃ_４ヘテロアルキル、または非芳香環から選ばれ；
Ｒ^７は、水素、場合により置換されたＣ_１〜Ｃ_８アルキル、場合により置換されたＣ_１〜Ｃ_８ハロアルキル、場合により置換されたＣ_１〜Ｃ_８ヘテロアルキル、場合により置換されたＣ１〜Ｃ_８ヘテロハロアルキル、場合により置換された芳香環、または(ＣＨ_２)_ｍＲ^１４から選ばれ；
Ｒ^１０は、水素、場合により置換されたＣ_１〜Ｃ_４アルキル、Ｃ_１〜Ｃ_４ハロアルキル、Ｃ_１〜Ｃ_４ヘテロアルキル、または非芳香環から選ばれ；
Ｒ^１１は、水素、ＳＯ_２Ｒ^１５、Ｃ_１〜Ｃ_４アルキル、Ｃ_１〜Ｃ_４ハロアルキル、Ｃ_１〜Ｃ_４ヘテロアルキル、または非芳香環から選ばれ；
Ｒ^１２およびＲ^１３は各々独立して、水素、場合により置換されたＣ_１〜Ｃ_４アルキル、場合により置換されたＣ_１〜Ｃ_４ハロアルキル、場合により置換されたＣ_１〜Ｃ_４ヘテロアルキル、場合により置換された非芳香環、または(ＣＨ_２)_ｍＲ^１４から選ばれるか；あるいは、Ｒ^１２およびＲ^１３の一方は場合により置換されたＣ_２〜Ｃ_６アルキルまたは場合により置換された非芳香環であって、そしてＲ^１２およびＲ^１３の他方はなしであるか；あるいは、Ｒ^１２およびＲ^１３は連結して場合により置換されたＣ_３〜Ｃ_８環を形成し；
Ｒ^１５は、水素、Ｃ_１〜Ｃ_３アルキル、Ｃ_１〜Ｃ_３ハロアルキル、またはアリールから選ばれ；
Ｙは、場合により置換されたＣ_１〜Ｃ_６アルキル、場合により置換されたＣ_１〜Ｃ_６ヘテロアルキル、場合により置換されたＣ_２〜Ｃ_６アルケニル、場合により置換されたＣ_２〜Ｃ_６ヘテロアルケニル、場合により置換されたフェニル、場合により置換されたヘテロアリール、場合により置換されたＣ_３〜Ｃ_５ヘテロ環、場合により置換されたシクロアルキル、または場合により置換されたシクロアルケニルから選ばれる１個以上の基を含有する、１〜４の原子数のスペーサーであり；そして、
Ｚは、
場合により置換されたＣ_６〜Ｃ_１０アリールもしくは場合により置換されたＣ_１〜Ｃ_８ヘテロアリールから選ばれる、２〜５の原子数のスペーサー、または、
場合により置換されたＣ_１〜Ｃ_６アルキル、場合により置換されたＣ_１〜Ｃ_６ヘテロアルキル、場合により置換されたＣ_１〜Ｃ_６ハロアルキル、場合により置換されたＣ_２〜Ｃ_６アルケニル、場合により置換されたＣ_２〜Ｃ_６ヘテロアルケニル、場合により置換されたＣ_２〜Ｃ_６ハロアルケニル、場合により置換されたＣ_２〜Ｃ_６アルキニル、もしくは場合により置換されたＣ_２〜Ｃ_６ヘテロアルキルから選ばれる、１〜５の原子数のスペーサー、
から選ばれる。 In certain embodiments, the present invention provides a compound of formula (I), or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof. here,
R ¹ is CO ₂ R ¹⁰ , CONR ¹⁰ R ¹¹ , SO ₃ R ¹⁰ , or tetrazole, NHSO ₂ R ¹⁵ , OC (S) NR ¹⁰ R ¹¹ , SC (O) NR ¹⁰ R ¹¹ , or a formula:

(Wherein A, B and C are each independently selected from O, S or N)
Selected from carboxylic acid biological equivalents selected from:
R ² and R ³ are each independently hydrogen, OR ¹² , NR ¹² R ¹³ , optionally substituted C ₁ -C ₄ alkyl, optionally substituted C ₁ -C ₄ haloalkyl, optionally substituted Selected from C ₁ -C ₄ heteroalkyl, optionally substituted ring, or (CH ₂ ) _m R ¹⁴ ; alternatively, R ² and R ³ together form an optionally substituted olefin Alternatively, R ² and R ³ are joined to form an optionally substituted C ₃ -C ₈ ring;
R ⁴ is selected from hydrogen, F, Cl, Br, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl, or a non-aromatic ring;
R ⁷ is hydrogen, optionally substituted C ₁ -C ₈ alkyl, optionally substituted C ₁ -C ₈ haloalkyl, optionally substituted C ₁ -C ₈ heteroalkyl, optionally substituted C 1- Selected from C ₈ heterohaloalkyl, optionally substituted aromatic ring, or (CH ₂ ) _m R ¹⁴ ;
R ¹⁰ is selected from hydrogen, optionally substituted C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl, or a non-aromatic ring;
R ¹¹ is selected from hydrogen, SO ₂ R ¹⁵ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl, or a non-aromatic ring;
R ¹² and R ¹³ are each independently hydrogen, optionally substituted C ₁ -C ₄ alkyl, optionally substituted C ₁ -C ₄ haloalkyl, optionally substituted C ₁ -C ₄ heteroalkyl, Selected from optionally substituted non-aromatic rings, or (CH ₂ ) _m R ¹⁴ ; alternatively, one of R ¹² and R ¹³ is optionally substituted C ₂ -C ₆ alkyl or optionally substituted non Is an aromatic ring and the other of R ¹² and R ¹³ is none; alternatively, R ¹² and R ¹³ are linked to form an optionally substituted C ₃ -C ₈ ring;
R ¹⁵ is selected from hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, or aryl;
Y is optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, optionally substituted C ₂ -C ₆ alkenyl, optionally substituted C ₂ -C ₆ Selected from heteroalkenyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted C ₃ -C ₅ heterocycle, optionally substituted cycloalkyl, or optionally substituted cycloalkenyl A spacer of 1 to 4 atoms containing one or more groups; and
Z is
Optionally selected from _C 1 -C ₈ heteroaryl, which are optionally substituted by a _C 6 _{-C 10} aryl or substituted, the number of 2 to 5 atom spacer, or,
Optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₂ -C ₆ alkenyl, if C ₂ -C ₆ heteroalkenyl substituted by, optionally substituted C ₂ -C ₆ haloalkenyl, optionally substituted C ₂ -C ₆ alkynyl, or optionally substituted C ₂ -C ₆ heteroalkyl A spacer of 1 to 5 atoms selected from
Chosen from.

［式中、
Ｒ^１は、ＣＯ_２Ｒ^１０、ＣＯＮＲ^１０Ｒ^１１、ＳＯ_３Ｒ^１０、またはカルボン酸生物学的等価体から選ばれ；
Ｒ^２およびＲ^３は各々独立して、なし、水素、ＯＲ^１２、ＮＲ^１２Ｒ^１３、場合により置換されたＣ_１〜Ｃ_４脂肪族、場合により置換されたＣ_１〜Ｃ_４ハロ脂肪族、場合により置換されたＣ_１〜Ｃ_４ヘテロ脂肪族、場合により置換された環、または(ＣＨ_２)_ｍＲ^１４から選ばれるか；あるいは、Ｒ^２およびＲ^３は一緒になって場合により置換されたオレフィンを形成するか；あるいは、Ｒ^２およびＲ^３は連結して場合により置換されたＣ_３〜Ｃ_８環を形成し；
Ｒ^４は、水素、Ｆ、Ｃｌ、Ｂｒ、Ｃ_１〜Ｃ_４脂肪族、Ｃ_１〜Ｃ_４ハロ脂肪族、Ｃ_１〜Ｃ_４ヘテロ脂肪族、または環から選ばれ；
Ｒ^５は、水素、ＯＲ^１０、ＳＲ^１０、ＮＨＲ^１１、またはＣＯ_２Ｈから選ばれ；
Ｒ^６は、水素、ＯＲ^１２、ＮＲ^１２Ｒ^１３、Ｆ、Ｃｌ、Ｂｒ、Ｃ_１〜Ｃ_４アルキル、Ｃ_１〜Ｃ_４ハロアルキル、Ｃ_１〜Ｃ_４ヘテロアルキル、または環から選ばれ；
Ｒ^７は、水素、場合により置換されたＣ_１〜Ｃ_８脂肪族、場合により置換されたＣ_１〜Ｃ_８ハロ脂肪族、場合により置換されたＣ_１〜Ｃ_８ヘテロ脂肪族、場合により置換されたＣ_１〜Ｃ_８ヘテロハロ脂肪族、場合により置換された環、または(ＣＨ_２)_ｍＲ^１４から選ばれ；
Ｒ^８およびＲ^９は各々独立して、水素、Ｆ、Ｃｌ、Ｂｒ、ＣＯ_２Ｒ^１０、ＮＯ_２、ＣＮ、ＳＯ_２Ｒ^１０、(ＣＨ_２)_ｍＲ^１４、Ｃ_１〜Ｃ_４脂肪族、Ｃ_１〜Ｃ_４ハロ脂肪族、Ｃ_１〜Ｃ_４ヘテロ脂肪族、Ｃ_１〜Ｃ_４ヘテロハロ脂肪族、または環から選ばれ；
Ｒ^１０は、水素、場合により置換されたＣ_１〜Ｃ_４脂肪族、Ｃ_１〜Ｃ_４ハロ脂肪族、Ｃ_１〜Ｃ_４ヘテロ脂肪族、または環から選ばれ；
Ｒ^１１は、水素、ＳＯ_２Ｒ^１５、Ｃ_１〜Ｃ_４脂肪族、Ｃ_１〜Ｃ_４ハロ脂肪族、Ｃ_１〜Ｃ_４ヘテロ脂肪族、または環から選ばれ；
Ｒ^１２およびＲ^１３は各々独立して、水素、場合により置換されたＣ_１〜Ｃ_４脂肪族、場合により置換されたＣ_１〜Ｃ_４ハロ脂肪族、場合により置換されたＣ_１〜Ｃ_４ヘテロ脂肪族、場合により置換された環、または(ＣＨ_２)_ｍＲ^１４から選ばれるか；あるいは、Ｒ^１２およびＲ^１３の一方は場合により置換されたＣ_２〜Ｃ_６脂肪族、または場合により置換された環であって、そしてＲ^１２およびＲ^１３の他方はなしであるか；あるいは、Ｒ^１２およびＲ^１３は連結して場合により置換されたＣ_３〜Ｃ_８環を形成し；
Ｒ^１４は、場合により置換されたアリールまたは場合により置換されたヘテロアリールから選ばれ；
Ｒ^１５は、水素、Ｃ_１〜Ｃ_３脂肪族、Ｃ_１〜Ｃ_３ハロ脂肪族、または環から選ばれ；
Ｑは、ＯまたはＳから選ばれ；
Ｘは、Ｏ、Ｓ、ＮＲ^１０、またはＣＲ^１０Ｒ^１０から選ばれ；
Ｙは、式：

から選ばれ；
Ｚは、
場合により置換されたＣ_６〜Ｃ_１０アリールもしくは場合により置換されたＣ_１〜Ｃ_８ヘテロアリールから選ばれる、２〜５の原子数のスペーサー、または、
場合により置換されたＣ_１〜Ｃ_６脂肪族、場合により置換されたＣ_１〜Ｃ_６ヘテロ脂肪族、もしくは場合により置換されたＣ_１〜Ｃ_６ハロ脂肪族から選ばれる、１〜５の原子数のスペーサー、
から選ばれ；
ｍは、０、１、または２であり；そして、
ｎは、０または１である］
で示される化合物、またはその医薬的に許容し得る塩、エステル、アミド、もしくはプロドラッグを提供する。 In certain embodiments, the present invention provides compounds of formula (II):

[Where:
R ¹ is selected from CO ₂ R ¹⁰ , CONR ¹⁰ R ¹¹ , SO ₃ R ¹⁰ , or a carboxylic acid biological equivalent;
R ² and R ³ are each independently none, hydrogen, OR ¹² , NR ¹² R ¹³ , optionally substituted C ₁ -C ₄ aliphatic, optionally substituted C ₁ -C ₄ haloaliphatic, Selected from optionally substituted C ₁ -C ₄ heteroaliphatic, optionally substituted ring, or (CH ₂ ) _m R ¹⁴ ; alternatively, R ² and R ^{3 taken} together are optionally substituted Or R ² and R ³ are joined to form an optionally substituted C ₃ -C ₈ ring;
R ⁴ is selected from hydrogen, F, Cl, Br, C ₁ -C ₄ aliphatic, C ₁ -C ₄ haloaliphatic, C ₁ -C ₄ heteroaliphatic, or a ring;
R ⁵ is selected from hydrogen, OR ¹⁰ , SR ¹⁰ , NHR ¹¹ , or CO ₂ H;
R ⁶ is selected from hydrogen, OR ¹² , NR ¹² R ¹³ , F, Cl, Br, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl, or a ring;
R ⁷ is hydrogen, optionally substituted C ₁ -C ₈ aliphatic, optionally substituted C ₁ -C ₈ haloaliphatic, optionally substituted C ₁ -C ₈ heteroaliphatic, optionally substituted Selected from C ₁ -C ₈ heterohaloaliphatic, optionally substituted rings, or (CH ₂ ) _m R ¹⁴ ;
R ⁸ and R ⁹ are each independently hydrogen, F, Cl, Br, CO ₂ R ¹⁰ , NO ₂ , CN, SO ₂ R ¹⁰ , (CH ₂ ) _m R ¹⁴ , C ₁ -C ₄ aliphatic, C ₁ -C _{4 haloaliphatic,} C 1 -C _{4 heteroaliphatic,} C 1 -C ₄ Heteroharo aliphatic or selected from a ring;
R ¹⁰ is selected from hydrogen, optionally substituted C ₁ -C ₄ aliphatic, C ₁ -C ₄ haloaliphatic, C ₁ -C ₄ heteroaliphatic, or a ring;
R ¹¹ is selected from hydrogen, SO ₂ R ¹⁵ , C ₁ -C ₄ aliphatic, C ₁ -C ₄ haloaliphatic, C ₁ -C ₄ heteroaliphatic, or a ring;
R ¹² and R ¹³ are each independently hydrogen, optionally substituted C ₁ -C ₄ aliphatic, optionally substituted C ₁ -C ₄ haloaliphatic, optionally substituted C ₁ -C ₄ Selected from heteroaliphatic, optionally substituted ring, or (CH ₂ ) _m R ¹⁴ ; alternatively, one of R ¹² and R ¹³ is optionally substituted C ₂ -C ₆ aliphatic, or optionally A substituted ring and the other of R ¹² and R ¹³ is none; alternatively, R ¹² and R ¹³ are joined to form an optionally substituted C ₃ -C ₈ ring;
R ¹⁴ is selected from optionally substituted aryl or optionally substituted heteroaryl;
R ¹⁵ is selected from hydrogen, C ₁ -C ₃ aliphatic, C ₁ -C ₃ haloaliphatic, or a ring;
Q is selected from O or S;
X is selected from O, S, NR ¹⁰ , or CR ¹⁰ R ¹⁰ ;
Y is the formula:

Chosen from;
Z is
Optionally selected from _C 1 -C ₈ heteroaryl, which are optionally substituted by a _C 6 _{-C 10} aryl or substituted, the number of 2 to 5 atom spacer, or,
1 to 5 atoms selected from optionally substituted C ₁ -C ₆ aliphatic, optionally substituted C ₁ -C ₆ heteroaliphatic, or optionally substituted C ₁ -C ₆ haloaliphatic Number of spacers,
Chosen from;
m is 0, 1, or 2; and
n is 0 or 1]
Or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof.

（式中、Ａ、ＢおよびＣは各々独立して、Ｏ、ＳまたはＮから選ばれる）
から選ばれるカルボン酸生物学的等価体、から選ばれ；
Ｒ^２およびＲ^３は各々独立して、水素、ＯＲ^１２、ＮＲ^１２Ｒ^１３、場合により置換されたＣ_１〜Ｃ_４アルキル、場合により置換されたＣ_１〜Ｃ_４ハロアルキル、場合により置換されたＣ_１〜Ｃ_４ヘテロアルキル、場合により置換された環、または(ＣＨ_２)_ｍＲ^１４から選ばれるか；あるいは、Ｒ^２およびＲ^３は一緒になって場合により置換されたオレフィンを形成するか；あるいは、Ｒ^２およびＲ^３は連結して場合により置換されたＣ_３〜Ｃ_８環を形成するか；あるいは、Ｒ^２またはＲ^３の一方はなく；
Ｒ^４は、水素、Ｆ、Ｃｌ、Ｂｒ、Ｃ_１〜Ｃ_４アルキル、Ｃ_１〜Ｃ_４ハロアルキル、Ｃ_１〜Ｃ_４ヘテロアルキル、または非芳香環から選ばれ；
Ｒ^７は、水素、場合により置換されたＣ_１〜Ｃ_８アルキル、場合により置換されたＣ_１〜Ｃ_８ハロアルキル、場合により置換されたＣ_１〜Ｃ_８ヘテロアルキル、場合により置換されたＣ_１〜Ｃ_８ヘテロハロアルキル、場合により置換された芳香環、または(ＣＨ_２)_ｍＲ^１４から選ばれ；
Ｒ^８およびＲ^９は各々独立して、水素、Ｆ、Ｃｌ、Ｂｒ、ＣＯ_２Ｒ^１０、ＮＯ_２、ＣＮ、ＳＯ_２Ｒ^１０、(ＣＨ_２)_ｍＲ^１４、Ｃ_１〜Ｃ_４アルキル、Ｃ_１〜Ｃ_４ハロアルキル、Ｃ_１〜Ｃ_４ヘテロアルキル、Ｃ_１〜Ｃ_４ヘテロハロアルキル、または環から選ばれ；
Ｒ^１０は、水素、場合により置換されたＣ_１〜Ｃ_４アルキル、Ｃ_１〜Ｃ_４ハロアルキル、Ｃ_１〜Ｃ_４ヘテロアルキル、または非芳香環から選ばれ；
Ｒ^１１は、水素、ＳＯ_２Ｒ^１５、Ｃ_１〜Ｃ_４アルキル、Ｃ_１〜Ｃ_４ハロアルキル、またはＣ_１〜Ｃ_４ヘテロアルキルから選ばれ；
Ｒ^１２およびＲ^１３は各々独立して、水素、場合により置換されたＣ_１〜Ｃ_４アルキル、場合により置換されたＣ_１〜Ｃ_４ハロアルキル、場合により置換されたＣ_１〜Ｃ_４ヘテロアルキル、場合により置換された非芳香環、または(ＣＨ_２)_ｍＲ^１４から選ばれるか；あるいは、Ｒ^１２およびＲ^１３の一方は場合により置換されたＣ_２〜Ｃ_６アルキルまたは場合により置換された非芳香環であって、そしてＲ^１２およびＲ^１３の他方はなしであるか；あるいは、Ｒ^１２およびＲ^１３は連結して場合により置換されたＣ_３〜Ｃ_８環を形成し；
Ｒ^１５は、水素、Ｃ_１〜Ｃ_３アルキル、Ｃ_１〜Ｃ_３ハロアルキル、またはアリールから選ばれ；そして、
Ｚは、
場合により置換されたＣ_６〜Ｃ_１０アリールもしくは場合により置換されたＣ_１〜Ｃ_８ヘテロアリールから選ばれる、２〜５の原子数のスペーサー、または、
場合により置換されたＣ_１〜Ｃ_６アルキル、場合により置換されたＣ_１〜Ｃ_６ヘテロアルキル、場合により置換されたＣ_１〜Ｃ_６ハロアルキル、場合により置換されたＣ_２〜Ｃ_６アルケニル、場合により置換されたＣ_２〜Ｃ_６ヘテロアルケニル、場合により置換されたＣ_２〜Ｃ_６ハロアルケニル、場合により置換されたＣ_２〜Ｃ_６アルキニル、もしくは場合により置換されたＣ_２〜Ｃ_６ヘテロアルキルから選ばれる、１〜５の原子数のスペーサー、
から選ばれる。 In certain embodiments, the present invention provides a compound of formula (II), or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof. here,
R ¹ is CO ₂ R ¹⁰ , CONR ¹⁰ R ¹¹ , SO ₃ R ¹⁰ , or tetrazole, NHSO ₂ R ¹⁵ , OC (S) NR ¹⁰ R ¹¹ , SC (O) NR ¹⁰ R ¹¹ , or a formula:

(Wherein A, B and C are each independently selected from O, S or N)
A carboxylic acid biological equivalent selected from:
R ² and R ³ are each independently hydrogen, OR ¹² , NR ¹² R ¹³ , optionally substituted C ₁ -C ₄ alkyl, optionally substituted C ₁ -C ₄ haloalkyl, optionally substituted Selected from C ₁ -C ₄ heteroalkyl, optionally substituted ring, or (CH ₂ ) _m R ¹⁴ ; alternatively, R ² and R ³ together form an optionally substituted olefin Or R ² and R ³ are joined to form an optionally substituted C ₃ -C ₈ ring; or there is no one of R ² or R ³ ;
R ⁴ is selected from hydrogen, F, Cl, Br, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl, or a non-aromatic ring;
R ⁷ is hydrogen, optionally substituted C ₁ -C ₈ alkyl, optionally substituted C ₁ -C ₈ haloalkyl, optionally substituted C ₁ -C ₈ heteroalkyl, optionally substituted C ₁ -C ₈ heteroalkyl haloalkyl, aromatic ring optionally substituted or (CH _2), is selected from _m R ^14;
R ⁸ and R ⁹ are each independently hydrogen, F, Cl, Br, CO ₂ R ¹⁰ , NO ₂ , CN, SO ₂ R ¹⁰ , (CH ₂ ) _m R ¹⁴ , C ₁ -C ₄ alkyl, C ₁ -C _{4 haloalkyl,} C 1 -C _{4 heteroalkyl,} selected from C 1 -C ₄ heteroalkyl haloalkyl or ring;
R ¹⁰ is selected from hydrogen, optionally substituted C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl, or a non-aromatic ring;
R ¹¹ is selected from hydrogen, SO ₂ R ¹⁵ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, or C ₁ -C ₄ heteroalkyl;
R ¹² and R ¹³ are each independently hydrogen, optionally substituted C ₁ -C ₄ alkyl, optionally substituted C ₁ -C ₄ haloalkyl, optionally substituted C ₁ -C ₄ heteroalkyl, Selected from optionally substituted non-aromatic rings, or (CH ₂ ) _m R ¹⁴ ; alternatively, one of R ¹² and R ¹³ is optionally substituted C ₂ -C ₆ alkyl or optionally substituted non Is an aromatic ring and the other of R ¹² and R ¹³ is none; alternatively, R ¹² and R ¹³ are linked to form an optionally substituted C ₃ -C ₈ ring;
R ¹⁵ is selected from hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, or aryl; and
Z is
Optionally selected from _C 1 -C ₈ heteroaryl, which are optionally substituted by a _C 6 _{-C 10} aryl or substituted, the number of 2 to 5 atom spacer, or,
Optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted C ₂ -C ₆ alkenyl, if C ₂ -C ₆ heteroalkenyl substituted by, optionally substituted C ₂ -C ₆ haloalkenyl, optionally substituted C ₂ -C ₆ alkynyl, or optionally substituted C ₂ -C ₆ heteroalkyl A spacer of 1 to 5 atoms selected from
Chosen from.

［式中、
Ｒ^１は、ＣＯ_２Ｒ^１０、ＣＯＮＲ^１０Ｒ^１１、ＳＯ_３Ｒ^１０、またはカルボン酸生物学的等価体から選ばれ；
Ｒ^２およびＲ^３は各々独立して、なし、水素、ＯＲ^１２、ＮＲ^１２Ｒ^１３、場合により置換されたＣ_１〜Ｃ_４脂肪族、場合により置換されたＣ_１〜Ｃ_４ハロ脂肪族、場合により置換されたＣ_１〜Ｃ_４ヘテロ脂肪族、場合により置換された環、または(ＣＨ_２)_ｍＲ^１４から選ばれるか；あるいは、Ｒ^２およびＲ^３は一緒になって場合により置換されたオレフィンを形成するか；あるいは、Ｒ^２およびＲ^３は連結して場合により置換されたＣ_３〜Ｃ_８環を形成し；
Ｒ^４は、水素、Ｆ、Ｃｌ、Ｂｒ、Ｃ_１〜Ｃ_４脂肪族、Ｃ_１〜Ｃ_４ハロ脂肪族、Ｃ_１〜Ｃ_４ヘテロ脂肪族、または環から選ばれ；
Ｒ^５は、水素、ＯＲ^１０、ＳＲ^１０、ＮＨＲ^１１、またはＣＯ_２Ｈから選ばれ；
Ｒ^６は、水素、ＯＲ^１２、ＮＲ^１２Ｒ^１３、Ｆ、Ｃｌ、Ｂｒ、Ｃ_１〜Ｃ_４アルキル、Ｃ_１〜Ｃ_４ハロアルキル、またはＣ_１〜Ｃ_４ヘテロアルキルから選ばれ；
Ｒ^７は、水素、場合により置換されたＣ_１〜Ｃ_８脂肪族、場合により置換されたＣ_１〜Ｃ_８ハロ脂肪族、場合により置換されたＣ_１〜Ｃ_８ヘテロ脂肪族、場合により置換されたＣ_１〜Ｃ_８ヘテロハロ脂肪族、場合により置換された環、または(ＣＨ_２)_ｍＲ^１４から選ばれ；
Ｒ^８およびＲ^９は各々独立して、水素、Ｆ、Ｃｌ、Ｂｒ、ＣＯ_２Ｒ^１０、ＮＯ_２、ＣＮ、ＳＯ_２Ｒ^１０、(ＣＨ_２)_ｍＲ^１４、Ｃ_１〜Ｃ_４脂肪族、Ｃ_１〜Ｃ_４ハロ脂肪族、Ｃ_１〜Ｃ_４ヘテロ脂肪族、またはＣ_１〜Ｃ_４ヘテロハロ脂肪族から選ばれ；
Ｒ^１０は、水素、場合により置換されたＣ_１〜Ｃ_４脂肪族、Ｃ_１〜Ｃ_４ハロ脂肪族、Ｃ_１〜Ｃ_４ヘテロ脂肪族、または環から選ばれ；
Ｒ^１１は、水素、ＳＯ_２Ｒ^１５、Ｃ_１〜Ｃ_４脂肪族、Ｃ_１〜Ｃ_４ハロ脂肪族、Ｃ_１〜Ｃ_４ヘテロ脂肪族、または環から選ばれ；
Ｒ^１２およびＲ^１３は各々独立して、水素、場合により置換されたＣ_１〜Ｃ_４脂肪族、場合により置換されたＣ_１〜Ｃ_４ハロ脂肪族、場合により置換されたＣ_１〜_Ｃ４ヘテロ脂肪族、場合により置換された環、または(ＣＨ_２)_ｍＲ^１４から選ばれるか；あるいは、Ｒ^１２およびＲ^１３の一方は場合により置換されたＣ_２〜Ｃ_６脂肪族、または場合により置換された環であって、そしてＲ^１２およびＲ^１３の他方はなしであるか；あるいは、Ｒ^１２およびＲ^１３は連結して場合により置換されたＣ_３〜Ｃ_８環を形成し；
Ｒ^１４は、場合により置換されたアリールまたは場合により置換されたヘテロアリールから選ばれ；
Ｒ^１５は、水素、Ｃ_１〜Ｃ_３脂肪族、Ｃ_１〜Ｃ_３ハロ脂肪族、または環から選ばれ；
ｍは、０、１、または２であり；そして、
ｎは、０または１である］
で示される化合物、またはその医薬的に許容し得る塩、エステル、アミド、もしくはプロドラッグを提供する。 In certain embodiments, the present invention provides compounds of formula (III):

[Where:
R ¹ is selected from CO ₂ R ¹⁰ , CONR ¹⁰ R ¹¹ , SO ₃ R ¹⁰ , or a carboxylic acid biological equivalent;
R ² and R ³ are each independently none, hydrogen, OR ¹² , NR ¹² R ¹³ , optionally substituted C ₁ -C ₄ aliphatic, optionally substituted C ₁ -C ₄ haloaliphatic, Selected from optionally substituted C ₁ -C ₄ heteroaliphatic, optionally substituted ring, or (CH ₂ ) _m R ¹⁴ ; alternatively, R ² and R ^{3 taken} together are optionally substituted Or R ² and R ³ are joined to form an optionally substituted C ₃ -C ₈ ring;
R ⁴ is selected from hydrogen, F, Cl, Br, C ₁ -C ₄ aliphatic, C ₁ -C ₄ haloaliphatic, C ₁ -C ₄ heteroaliphatic, or a ring;
R ⁵ is selected from hydrogen, OR ¹⁰ , SR ¹⁰ , NHR ¹¹ , or CO ₂ H;
R ⁶ is selected from hydrogen, OR ¹² , NR ¹² R ¹³ , F, Cl, Br, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, or C ₁ -C ₄ heteroalkyl;
R ⁷ is hydrogen, optionally substituted C ₁ -C ₈ aliphatic, optionally substituted C ₁ -C ₈ haloaliphatic, optionally substituted C ₁ -C ₈ heteroaliphatic, optionally substituted Selected from C ₁ -C ₈ heterohaloaliphatic, optionally substituted rings, or (CH ₂ ) _m R ¹⁴ ;
R ⁸ and R ⁹ are each independently hydrogen, F, Cl, Br, CO ₂ R ¹⁰ , NO ₂ , CN, SO ₂ R ¹⁰ , (CH ₂ ) _m R ¹⁴ , C ₁ -C ₄ aliphatic, C ₁ -C _{4 haloaliphatic,} C 1 -C ₄ heteroaliphatic, or selected from _C 1 -C ₄ Heteroharo aliphatic;
R ¹⁰ is selected from hydrogen, optionally substituted C ₁ -C ₄ aliphatic, C ₁ -C ₄ haloaliphatic, C ₁ -C ₄ heteroaliphatic, or a ring;
R ¹¹ is selected from hydrogen, SO ₂ R ¹⁵ , C ₁ -C ₄ aliphatic, C ₁ -C ₄ haloaliphatic, C ₁ -C ₄ heteroaliphatic, or a ring;
R ¹² and ^{R 13} are each independently hydrogen, optionally _C 1 -C ₄ substituted aliphatic, optionally _C 1 -C ₄ halo substituted aliphatic, _C 1 _{~ C4} heteroaryl optionally substituted Selected from aliphatic, optionally substituted ring, or (CH ₂ ) _m R ¹⁴ ; or one of R ¹² and R ¹³ is optionally substituted C ₂ -C ₆ aliphatic, or optionally substituted And the other of R ¹² and R ¹³ is none; alternatively, R ¹² and R ¹³ are linked to form an optionally substituted C ₃ -C ₈ ring;
R ¹⁴ is selected from optionally substituted aryl or optionally substituted heteroaryl;
R ¹⁵ is selected from hydrogen, C ₁ -C ₃ aliphatic, C ₁ -C ₃ haloaliphatic, or a ring;
m is 0, 1, or 2; and
n is 0 or 1]
Or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof.

（式中、Ａ、ＢおよびＣは各々独立して、Ｏ、ＳまたはＮから選ばれる）
から選ばれるカルボン酸生物学的等価体、から選ばれ；
Ｒ^２およびＲ^３は各々独立して、水素、ＯＲ^１２、ＮＲ^１２Ｒ^１３、場合により置換されたＣ_１〜Ｃ_４アルキル、場合により置換されたＣ_１〜Ｃ_４ハロアルキル、場合により置換されたＣ_１〜Ｃ_４ヘテロアルキル、場合により置換された環、または(ＣＨ_２)_ｍＲ^１４から選ばれるか；あるいは、Ｒ^２およびＲ^３は一緒になって場合により置換されたオレフィンを形成するか；あるいは、Ｒ^２およびＲ^３は連結して場合により置換されたＣ_３〜Ｃ_８環を形成し；
Ｒ^４は、水素、Ｆ、Ｃｌ、Ｂｒ、Ｃ_１〜Ｃ_４アルキル、Ｃ_１〜Ｃ_４ハロアルキル、Ｃ_１〜Ｃ_４ヘテロアルキル、または非芳香環から選ばれ；
Ｒ^７は、水素、場合により置換されたＣ_１〜Ｃ_８アルキル、場合により置換されたＣ_１〜Ｃ_８ハロアルキル、場合により置換されたＣ_１〜Ｃ_８ヘテロアルキル、場合により置換されたＣ_１〜Ｃ_８ヘテロハロアルキル、場合により置換された芳香環、または(ＣＨ_２)_ｍＲ^１４から選ばれ；
Ｒ^８およびＲ^９は各々独立して、水素、Ｆ、Ｃｌ、Ｂｒ、ＣＯ_２Ｒ^１０、ＮＯ_２、ＣＮ、ＳＯ_２Ｒ^１０、(ＣＨ_２)_ｍＲ^１４、Ｃ_１〜Ｃ_４アルキル、Ｃ_１〜Ｃ_４ハロアルキル、Ｃ_１〜Ｃ_４ヘテロアルキル、またはＣ_１〜Ｃ_４ヘテロハロアルキルから選ばれ；
Ｒ^１０は、水素、場合により置換されたＣ_１〜Ｃ_４アルキル、Ｃ_１〜Ｃ_４ハロアルキル、Ｃ_１〜Ｃ_４ヘテロアルキル、または非芳香環から選ばれ；
Ｒ^１１は、水素、ＳＯ_２Ｒ^１５、Ｃ_１〜Ｃ_４アルキル、Ｃ_１〜Ｃ_４ハロアルキル、Ｃ_１〜Ｃ_４ヘテロアルキル、または非芳香環から選ばれ；
Ｒ^１２およびＲ^１３は各々独立して、水素、場合により置換されたＣ_１〜Ｃ_４アルキル、場合により置換されたＣ_１〜Ｃ_４ハロアルキル、場合により置換されたＣ_１〜Ｃ_４ヘテロアルキル、非芳香環、または(ＣＨ_２)_ｍＲ^１４から選ばれるか；あるいは、Ｒ^１２およびＲ^１３の一方は場合により置換されたＣ_２〜Ｃ_６アルキルまたは非芳香環であって、そしてＲ^１２およびＲ^１３の他方はなしであるか；あるいは、Ｒ^１２およびＲ^１３は連結して場合により置換されたＣ_３〜Ｃ_８環を形成し；そして、
Ｒ^１５は、水素、Ｃ_１〜Ｃ_３アルキル、Ｃ_１〜Ｃ_３ハロアルキル、またはアリールから選ばれる。 In certain embodiments, the present invention provides a compound of formula (III), or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof. here,
R ¹ is CO ₂ R ¹⁰ , CONR ¹⁰ R ¹¹ , SO ₃ R ¹⁰ , or tetrazole, NHSO ₂ R ¹⁵ , OC (S) NR ¹⁰ R ¹¹ , SC (O) NR ¹⁰ R ¹¹ , or a formula:

(Wherein A, B and C are each independently selected from O, S or N)
A carboxylic acid biological equivalent selected from:
R ² and R ³ are each independently hydrogen, OR ¹² , NR ¹² R ¹³ , optionally substituted C ₁ -C ₄ alkyl, optionally substituted C ₁ -C ₄ haloalkyl, optionally substituted Selected from C ₁ -C ₄ heteroalkyl, optionally substituted ring, or (CH ₂ ) _m R ¹⁴ ; alternatively, R ² and R ³ together form an optionally substituted olefin Alternatively, R ² and R ³ are joined to form an optionally substituted C ₃ -C ₈ ring;
R ⁴ is selected from hydrogen, F, Cl, Br, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl, or a non-aromatic ring;
R ⁷ is hydrogen, optionally substituted C ₁ -C ₈ alkyl, optionally substituted C ₁ -C ₈ haloalkyl, optionally substituted C ₁ -C ₈ heteroalkyl, optionally substituted C ₁ -C ₈ heteroalkyl haloalkyl, aromatic ring optionally substituted or (CH _2), is selected from _m R ^14;
R ⁸ and R ⁹ are each independently hydrogen, F, Cl, Br, CO ₂ R ¹⁰ , NO ₂ , CN, SO ₂ R ¹⁰ , (CH ₂ ) _m R ¹⁴ , C ₁ -C ₄ alkyl, C Selected from ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl, or C ₁ -C ₄ heterohaloalkyl;
R ¹⁰ is selected from hydrogen, optionally substituted C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl, or a non-aromatic ring;
R ¹¹ is selected from hydrogen, SO ₂ R ¹⁵ , C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, C ₁ -C ₄ heteroalkyl, or a non-aromatic ring;
R ¹² and R ¹³ are each independently hydrogen, optionally substituted C ₁ -C ₄ alkyl, optionally substituted C ₁ -C ₄ haloalkyl, optionally substituted C ₁ -C ₄ heteroalkyl, A non-aromatic ring, or (CH ₂ ) _m R ¹⁴ ; alternatively, one of R ¹² and R ¹³ is an optionally substituted C ₂ -C ₆ alkyl or non-aromatic ring, and R ¹² and The other of R ¹³ is none; alternatively, R ¹² and R ¹³ are linked to form an optionally substituted C ₃ -C ₈ ring; and
R ¹⁵ is selected from hydrogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, or aryl.

  In certain embodiments, the compound of Formula I, II, or III is a selective TPO modifier. In certain such embodiments, the compound of Formula I, II, or III is a TPO mimetic.

  In certain embodiments, the present invention provides selective TPO modifiers. In certain embodiments, the present invention provides selective TPO receptor agonists. In certain embodiments, the present invention provides selective TPO receptor antagonists. In certain embodiments, the present invention provides selective TPO partial agonists. In certain embodiments, the present invention provides selective TPO receptor binding compounds. In certain embodiments, the present invention provides TPO mimetics. In certain embodiments, the present invention provides tissue-selective selective TPO modulators.

  In certain embodiments, the present invention provides a method of modulating TPO activity. The method includes contacting the cell with one or more compounds of the invention. The method includes, but is not limited to, contacting TPO and / or TPO receptor with one or more compounds of the present invention.

  In certain embodiments, the present invention identifies compounds capable of modulating TPO activity comprising contacting a cell having the ability of TPO activity with a compound of the present invention and tracking the effect on the cell. Provide a method. In certain such embodiments, the cell expresses a TPO receptor.

  In certain embodiments, the present invention provides a method of treating a patient comprising administering a compound of the present invention to the patient. In certain embodiments, the patient suffers from thrombocytopenia. In certain embodiments, one or more compounds of the invention are administered to a patient before, during, or after chemotherapy, bone marrow transplantation, and / or radiation therapy. In certain embodiments, one or more compounds of the invention are administered to a patient suffering from aplastic anemia, bone marrow dysfunction, and / or idiopathic thrombocytopenia. In certain embodiments, one or more compounds of the invention are administered to a patient suffering from a nervous system disorder. In certain embodiments, one or more compounds of the invention are administered to a patient suffering from amyotrophic lateral sclerosis, multiple sclerosis, or multiple dystrophy. In certain embodiments, one or more compounds of the present invention are administered to a patient having a nerve injury, including but not limited to spinal cord injury.

  In certain embodiments, the present invention provides a pharmaceutical composition comprising one or more compounds of the present invention and a physiologically acceptable carrier, diluent or excipient.

(Detailed description of preferred embodiments)
It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention as claimed. In this specification, the use of the singular includes the plural unless specifically stated otherwise. Unless otherwise specified, the use of “or” herein means “and / or”. Moreover, the use of the term “contains”, as well as other forms (eg, “includes” and “included”) is not limiting.

  The section headings herein are for organizational purposes only and are not to be construed as limiting the subject matter described. All documents cited in this application, or parts of documents (eg, including but not limited to patents, patent applications, articles, books, manuals, and papers) may be used for any purpose in this specification. Explicitly incorporated by reference for those complete.

(Definition)
Unless otherwise specified, the nomenclature used in combination herein, as well as the laboratory methods and techniques, analytical chemistry, synthetic organic chemistry, medicine and pharmaceuticals described herein. Chemistry is knowledge well known in the art. Standard chemical symbols are used interchangeably with the full nomenclature indicated by the symbols. Thus, the terms “hydrogen” and “H” are understood to have the same meaning. Standard techniques for chemical synthesis, chemical analysis, pharmaceutical manufacturing, formulation, delivery, and patient treatment can be used. Standard techniques for recombinant DNA, oligonucleotide synthesis, and tissue culture and transformation (eg, electroporation, lipofection) can be used. Reaction and purification techniques can be performed using kits, for example, according to commercial specifications, or as commonly accomplished in the art or as described herein. The techniques and methods described above are generally in accordance with conventional methods well known in the art, and in various general and more specific cited references, which are cited and described throughout this specification. Can be carried out as described in. For example, Sambrook et al., Molecular Cloning: A Laboratory Manual (2nd edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY (1989)), which forms part of this place. reference.

  The following terms used herein are defined to have the following meanings unless otherwise specified.

  The term “a compound that selectively binds” refers to a compound that selectively binds to any part of one or more targets.

  The term “selective TPO receptor binding compound” means a compound that selectively binds to any portion of the TPO receptor.

  The term “selectively binds” refers to the ability of a selectively binding compound to bind to a target receptor with greater affinity than it binds to a non-target receptor. In certain embodiments, specific binding means binding to the target with an affinity that is at least 10, 50, 100, 250, 500, or 1000 times greater than the affinity for the non-target.

  The term “target receptor” means a receptor or portion of a receptor that can be bound by a compound that selectively binds. In certain embodiments, the target receptor is a TPO receptor.

  The term “modulator” means a compound that alters or induces activity. For example, the presence of a modifying substance can result in an increase or decrease in the magnitude of activity compared to the magnitude of activity in the absence of the modifying substance. In certain embodiments, the modifying agent is an inhibitor, which reduces the magnitude of one or more activities. In certain embodiments, the inhibitor completely prevents one or more biological activities. In certain embodiments, the modifier is an activator, which increases the magnitude of at least one activity. In certain embodiments, the presence of the modifier results in an activity that does not occur in the absence of the modifier.

  The term “selective modifier” means a compound that selectively modulates a target activity.

  The term “selective TPO modulator” means a compound that selectively modulates at least one TPO activity. The term “selective TPO modulator” includes, but is not limited to, a “TPO mimetic” (which means a compound that, in its presence, produces at least one TPO activity).

  The term “selectively modulates” means the ability of a selective modulator to modulate target activity to a greater extent than it modulates non-target activity.

  The term “target activity” means a biological activity that can be modulated by a selective modifier. Typical target activities include: binding affinity; signal transduction; enzyme activity; transcription of one or more genes; proliferation and / or differentiation of cells (including but not limited to progenitor cells); platelet production Including, but not limited to, alleviating the symptoms of the disease or condition.

  The term “TPO activity” means a biological activity that occurs either directly or indirectly from the presence of TPO. Typical TPO activities include, but are not limited to, platelet production by progenitor cell proliferation and / or differentiation; hematopoiesis; glial cell proliferation and / or differentiation; nerve cell repair; and reduction of thrombocytopenia. It is not limited.

  The term “thrombocytopenia” means a disease in which the concentration of platelets in the patient's blood is below that which is considered normal for a healthy patient. In certain embodiments, thrombocytopenia has a platelet count of 450,000, 400,000, 350,000, 300,000, 250,000, 200,000, 150,000, 140,000 per microliter of blood. , 130,000, 120,000, 110,000, 100,000, 75,000, or 50,000 platelet counts.

  The term “receptor mediated activity” means any biological activity that results either directly or indirectly from binding of a ligand to a receptor.

  The term “agonist” means a compound that, by its presence, produces a biological activity of the receptor that is the same as the biological activity that results from the presence of the natural ligand for the receptor.

  The term “partial agonist” means a compound whose presence results in the biological activity of the receptor of the same type but with a smaller size that results from the presence of the natural ligand for the receptor. To do.

  The term “antagonist” means a compound that, by its presence, provides a reduction in the magnitude of the biological activity of the receptor. In certain embodiments, the presence of an antagonist results in complete inhibition of the biological activity of the receptor.

  The term “aliphatic”, alone or in combination, means a straight chain or branched chain containing at least one carbon atom. Aliphatic includes alkyl, alkenyl, and alkynyl. In certain embodiments, the aliphatic is optionally substituted. Aliphatic means methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl, hexyl, ethenyl, propenyl, butenyl, ethynyl, butynyl, propynyl, etc. (each of which may be optionally substituted) Including, but not limited to. As described herein, aliphatic is not intended to include cyclic groups.

The term “alkyl”, alone or in combination, means a fully saturated aliphatic. In certain embodiments, the alkyl is optionally substituted. In certain embodiments, alkyl represents 1 to 20 carbons, which are indicated herein by any numerical range (eg, “1-20” or “C ₁ -C ₂₀ ”, which are Means each integer in the range; for example, “C ₁ -C ₂₀ ” contains no more than 20 carbon atoms, such as only 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc. Examples of alkyl are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, tert-amyl, pentyl, hexyl, heptyl, octyl. Including, but not limited to.

  The term “alkenyl”, alone or in combination, signifies an aliphatic having one or more carbon-carbon double bonds. In certain embodiments, alkenyl is optionally substituted. Examples of alkenyl include, but are not limited to, ethenyl, propenyl, 1,4-butadienyl, and the like.

  The term “alkynyl”, alone or in combination, means an aliphatic having one or more carbon-carbon triple bonds. In certain embodiments, alkynyl is optionally substituted. Examples of alkynyl include, but are not limited to, ethynyl, propynyl, butynyl and the like.

  The term “haloaliphatic”, alone or in combination, means an aliphatic in which at least one hydrogen atom is replaced with a halogen atom. In certain embodiments in which two or more hydrogen atoms are replaced with halogen atoms, the halogen atoms are all the same as one another. In certain embodiments, the halogen atoms are not all the same as each other. Haloaliphatic includes haloalkyl, haloalkenyl, and haloalkynyl. In certain embodiments, the haloaliphatic is optionally substituted in addition to hydrogen / halogen substitution. The term “haloaliphatic” also includes perhaloaliphatics in which all of the aliphatic hydrogen atoms are replaced with halogen atoms. Examples of perhaloaliphatics include trichloromethyl, pentachloroethyl and the like.

The term “heteroaliphatic”, alone or in combination, signifies a group containing aliphatic and one or more heteroatoms. Some heteroaliphatics are acyl aliphatics in which one or more heteroatoms are not present in the aliphatic chain. Heteroaliphatic includes heteroalkyl (eg, including but not limited to acylalkyl); heteroalkenyl (eg, including but not limited to acylalkenyl); and heteroalkynyl (eg, including acylalkynyl). Including, but not limited to). Examples of heteroaliphatic are CH ₃ C (═O) CH ₂ —, CH ₃ C (═O) CH ₂ CH ₂ —, CH ₃ CH ₂ C (═O) CH ₂ CH ₂ —, CH ₃ C ( ═O) CH ₂ CH ₂ CH ₂ —, CH ₃ OCH ₂ CH ₂ —, CH ₃ NHCH ₂ — and the like. In certain embodiments, the heteroaliphatic is optionally substituted.

  The term “heterohaloaliphatic” means a heteroaliphatic in which at least one hydrogen atom is replaced with a halogen atom. Heterohaloaliphatic includes heterohaloalkyl, heterohaloalkenyl, and heteroalkynyl. In certain embodiments, the heterohaloaliphatic is optionally substituted.

を形成する場合には、得られる構造は、式：

（式中、Ｒ'''およびＲ''''は水素である）
である。上記のＲ'''およびＲ''''が独立して水素および任意の置換基から選ばれる場合には、オレフィンは場合により置換され得る。 The term “olefin” means a C═C bond. The term “together to form an olefin” means that two groups are bonded to the same atom and one of the two groups is ═C and the other of the two groups is absent. (null) means the case. For example, R ′ and R ″ in the following structure are taken together to form an olefin:

The resulting structure is of the formula:

(Where R ′ ″ and R ″ ″ are hydrogen)
It is. If the above R ″ ′ and R ″ ″ are independently selected from hydrogen and optional substituents, the olefin may be optionally substituted.

  The term “carbocycle” means a group containing a covalently closed ring wherein each of the atoms forming the ring is a carbon atom. A carbocycle may be formed by 3, 4, 5, 6, 7, 8, 9, or more than 9 carbon atoms. The carbocycle can be optionally substituted.

（式中、Ｄ、Ｅ、ＦおよびＧは独立してヘテロ原子である）
を含むが、これらに限定されない。Ｄ、Ｅ、ＦおよびＧの各々は、互いに同じかまたは異なってもよい。 The term “heterocycle” refers to a group containing a covalently closed ring in which at least one atom forming the ring is a carbon atom and at least one atom forming the ring is a heteroatom. Means. Heterocycles can be formed by 3, 4, 5, 6, 7, 8, 9, or more than 9 atoms. Any number of these atoms can be a heteroatom (ie, a heterocycle can comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, or more than 9 heteroatoms). In the present specification, whenever the number of carbon atoms in a heterocycle is indicated (eg, a C ₁ -C ₆ heterocycle), at least one other atom (heteroatom) is present in the ring. Must exist. For example, a designation such as “C ₁ -C ₆ heterocycle” means only the number of carbon atoms in the ring and does not mean the total number of atoms in the ring. A heterocycle is understood to have additional heteroatoms in the ring. In heterocycles containing two or more heteroatoms, the two or more heteroatoms may be the same or different from one another. Heterocycles can be optionally substituted. The bond to the heterocycle can be on a heteroatom or through a carbon atom. Examples of heterocycles have the following formula:

(Wherein D, E, F and G are independently heteroatoms)
Including, but not limited to. Each of D, E, F and G may be the same or different from each other.

  The term “heteroatom” means an atom other than carbon or hydrogen. Heteroatoms are typically independently selected from oxygen, sulfur, nitrogen, or phosphorus, but are not limited to these atoms. In embodiments where two or more heteroatoms are present, the two or more heteroatoms may all be the same as each other, or some or all of the two or more heteroatoms may be different from each other.

The term “aromatic” refers to a group containing a covalently closed planar ring having a delocalized π-electron system containing 4n + 2π electrons, where n is an integer. Aromatic rings can be formed by 5, 6, 7, 8, 9, or more than 9 atoms. Aromatic rings can be optionally substituted. Examples of aromatic ring groups include, but are not limited to, phenyl, naphthalenyl, phenanthrenyl, anthracenyl, tetralinyl, fluorenyl, indenyl, indanyl. The term “aromatic ring” includes, for example, benzenoid groups linked by one of the carbon atoms forming the ring and optionally having one or more substituents. The substituent is aryl, heteroaryl, cycloalkyl, non-aromatic heterocycle, halo, hydroxy, amino, cyano, nitro, alkylamide, acyl, C _1-6 alkoxy, C _1-6 alkyl, C _{1- It is selected from 6} hydroxyalkyl, C _1-6 aminoalkyl, C _1-6 alkylamino, alkylsulfenyl, alkylsulfinyl, alkylsulfonyl, sulfamoyl, or trifluoromethyl. In certain embodiments, the aromatic ring group is substituted at one or more of the para, meta, and / or ortho positions. Examples of aromatic ring groups containing substituents are phenyl, 3-halophenyl, 4-halophenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 3-aminophenyl, 4-aminophenyl, 3-methylphenyl, 4-methyl. Phenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-trifluoromethoxyphenyl, 3-cyanophenyl, 4-cyanophenyl, dimethylphenyl, naphthyl, hydroxynaphthyl, hydroxymethylphenyl, (trifluoromethyl) phenyl, alkoxyphenyl , 4-morpholin-4-ylphenyl, 4-pyrrolidin-1-ylphenyl, 4-pyrazolylphenyl, 4-triazolylphenyl, and 4- (2-oxopyrrolidin-1-yl) phenyl, It is not limited to.

  The term “aryl” means an aromatic ring in which each of the atoms forming the ring is a carbon atom. The aryl ring can be formed by 5, 6, 7, 8, 9, or more than 9 carbon atoms. The aryl group can be optionally substituted.

The term “heteroaryl” refers to an aromatic heterocycle. A heteroaryl ring can be formed by 3, 4, 5, 6, 7, 8, 9, or more than 9 atoms. Heteroaryl can be optionally substituted. Examples of heteroaryl groups are one oxygen or sulfur atom or a nitrogen atom up to four or one oxygen or aromatic C ₃ ~ ₈ hetero containing a combination of nitrogen atoms to sulfur atoms and two, Including, but not limited to, ring groups, and substituted groups thereof, as well as benzo- and pyrido-fused derivatives (eg, linked by one of the carbon atoms forming the ring). In certain embodiments, the heteroaryl group is optionally substituted with one or more substituents. The substituent is independently halo, hydroxy, amino, cyano, nitro, alkylamide, acyl, C _1-6 alkoxy, C _1-6 alkyl, C _1-6 -hydroxyalkyl, C _{1-6 -aminoalkyl.} , C _1-6 -alkylamino, alkylsulfenyl, alkylsulfinyl, alkylsulfonyl, sulfamoyl, or trifluoromethyl. Examples of heteroaryl groups are furan, benzofuran, thiophene, benzothiophene, pyrrole, pyridine, indole, oxazole, benzoxazole, isoxazole, benzisoxazole, thioazole, benzothiazole, isothiazole, imidazole, benzimidazole, pyrazole, indazole Tetrazole, quinoline, isoquinoline, pyridazine, pyrimidine, purine, pyrazine, furazane, 1,2,3-oxadiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole, triazole, benzotriazole, pteridine, Includes unsubstituted and mono- or di-substituted derivatives of phenoxazole, oxadiazole, benzopyrazole, quinolidine, cinnoline, phthalazine, quinazoline, and quinoxaline But, but it is not limited to these. In certain embodiments, the substituents are halo, hydroxy, cyano, O—C _1-6 -alkyl, C _1-6 -alkyl, hydroxy-C _1-6 -alkyl, and amino-C _1-6 -alkyl. is there.

  The term “non-aromatic ring” means a group containing a covalently closed ring that is not aromatic.

  The term “alicyclic” means a group containing a non-aromatic ring in which each of the atoms forming the ring is a carbon atom. An alicyclic ring can be formed by 3, 4, 5, 6, 7, 8, 9, or more than 9 carbon atoms. In certain embodiments, the alicyclic is optionally substituted. In certain embodiments, the cycloaliphatic contains one or more unsaturated bonds. Alicyclic includes cycloalkyl, cycloalkenyl, and cycloalkynyl. Examples of alicyclics include, but are not limited to, cyclopropane, cyclobutane, cyclopentane, cyclopentene, cyclopentadiene, cyclohexane, cyclohexene, 1,3-cyclohexadiene, 1,4-cyclohexadiene, cycloheptane, and cycloheptene. Not. In certain embodiments, the alicyclic ring is optionally substituted.

  The term “non-aromatic heterocycle” means a group containing a non-aromatic ring in which one or more of the atoms forming the ring is a heteroatom. Non-aromatic heterocycles can be formed by 3, 4, 5, 6, 7, 8, 9, or more than 9 atoms. Non-aromatic heterocycles can be optionally substituted. In some embodiments, the non-aromatic heterocycle contains one or more carbonyl or thiocarbonyl groups (eg, oxo- and thio-containing groups). Examples of non-aromatic heterocycles are lactam, lactone, cyclic imide, cyclic thioimide, cyclic carbamate, tetrahydrothiopyran, 4H-pyran, tetrahydropyran, piperidine, 1,3-dioxin, 1,3-dioxane, 1, 4-dioxin, 1,4-dioxane, piperazine, 1,3-oxathiane, 1,4-oxathiin, 1,4-oxathiane, tetrahydro-1,4-thiazine, 2H-1,2-oxazine, maleimide, succinimide, Barbituric acid, thiobarbituric acid, dioxopiperazine, hydantoin, dihydrouracil, morpholine, thioxane, hexahydro-1,3,5-triazine, tetrahydrothiophene, tetrahydrofuran, pyrroline, pyrrolidine, pyrrolidone, pyrrolidione, pyrazoline, pyrazolidine, imida Phosphorus, imidazolidine, 1,3-dioxole, 1,3-dioxolane, 1,3-dithiol, 1,3-dithiolane, isoxazoline, isoxazolidine, oxazoline, oxazolidine, oxazolidinone, thiazoline, thiazolidine, and 1,3-oxathiolane Including, but not limited to.

  The term “arylalkyl” refers to a group containing an aryl group bonded to an alkyl group.

  The term “ring” means any covalently closed ring structure. Rings include, for example, carbocycles (eg, aryl and alicyclic), heterocycles (eg, heteroaryl and non-aromatic heterocycles), aromatic rings (eg, aryl and heteroaryl), and non-aromatic rings (eg, Alicyclic and non-aromatic heterocycles). Rings can be optionally substituted. The ring may form a cyclic moiety.

  The term “cyclic” means two or more rings in which two or more rings are fused. The term “fused” refers to a structure in which two or more rings share one or more bonds.

において、ＸがＮである例には、ＸがＮであり、Ｒ'またはＲ''の１つはなしであって、これは、３個の基だけがＮと結合することを意味する。 The term “null” means a group that is not present in the structure. For example, the structure:

In the example where X is N, X is N and one of R ′ or R ″ is absent, meaning that only three groups are attached to N.

（式中、Ａ、ＢおよびＣは各々独立して、Ｏ、ＳまたはＮから選ばれる）
を含む。 The term “carboxyclic acid bioisoster” means a group that is biologically equivalent to a carboxylic acid. For example, carboxylic acid bioequivalents include tetrazole, NHSO ₂ R ¹⁵ , OC (S) NR ¹⁰ R ¹¹ , SC (O) NR ¹⁰ R ¹¹ , thiazolidinedione, oxazolidinedione, and 1-oxa-2, Including, but not limited to, 4-diazolidine-3,5-dione. In some embodiments, the carboxylic acid bioequivalent has the following structure:

(Wherein A, B and C are each independently selected from O, S or N)
including.

  The term “spacer” means an atom or group of atoms in which two or more groups are separated from each other by the desired number of atoms. For example, in certain embodiments, it may be desirable for two or more groups to be separated by more than 1, 2, 3, 4, 5, 6, or 6 atoms. In such embodiments, any atom or group of atoms can be used to separate the group by the desired number of atoms. In certain embodiments, the spacer can be optionally substituted. In certain embodiments, the spacer comprises an aliphatic. In certain embodiments, the spacer comprises an atom that is part of a ring.

（式中、ＡおよびＢは、所望する数の原子によって分離される基である）
を含むが、これらに限定されない。２−原子数のスペーサーの例は、以下の式：

（式中、ＡおよびＢは、所望する数の原子によって分離される基である）
を含むが、これらに限定されない。３−原子数のスペーサーの例は、以下の式：

（式中、ＡおよびＢは、所望する数の原子によって分離される基である）
を含むが、これらに限定されない。 For purposes of illustration only and without limiting the above definitions, examples of spacers are provided. An example of a one-atom spacer is the following formula:

Where A and B are groups separated by the desired number of atoms.
Including, but not limited to. Examples of 2-atom spacers are:

Where A and B are groups separated by the desired number of atoms.
Including, but not limited to. An example of a 3-atomic spacer is the following formula:

Where A and B are groups separated by the desired number of atoms.
Including, but not limited to.

（式中、Ｑは１−原子数のスペーサーである）
において、生成する環は、Ａ、ＢおよびＱ（ここで、Ｑは場合により置換され得る）を含有する３員環である。該構造の例は、式：

を含むが、これらに限定されない。例えば、Ｑが２−原子数のスペーサーである場合には、４員環を生じ；Ｑが３−原子数のスペーサーである場合には、５員環を生じ；Ｑが４−原子数のスペーサーである場合には、６員環を生じ；；Ｑが５−原子数のスペーサーである場合には、７員環を生じ；Ｑが６−原子数のスペーサーである場合には、８員環を生じる。ある実施態様において、環中のスペーサーは、スペーサーによって形成される環およびスペーサーを含む環が縮合するように、環を含む。例えば、Ｑが縮合環を含有する３−原子数のスペーサーである上記の構造について言及する場合には、構造：

（式中、縮合環はスペーサーのいずれかの結合で縮合し得る）
を含むが、これらに限定されない。該縮合環は場合により置換され得て、そして、これはヘテロ環または炭素環であり得る。 In certain embodiments, the spacer separates the atoms in the ring. For example, the structure:

(Where Q is a 1-atom spacer)
The ring produced is a three-membered ring containing A, B and Q, where Q may be optionally substituted. An example of the structure is the formula:

Including, but not limited to. For example, if Q is a 2-atom spacer, a 4-membered ring is formed; if Q is a 3-atom spacer, a 5-membered ring is formed; Q is a 4-atom spacer When Q is a 5-atom spacer, a 7-membered ring is produced; when Q is a 6-atom spacer, an 8-membered ring is produced. Produce. In certain embodiments, the spacer in the ring comprises a ring such that the ring formed by the spacer and the ring comprising the spacer are fused. For example, when referring to the above structure where Q is a 3-atomic spacer containing a fused ring, the structure:

(Wherein the fused ring can be fused at any bond of the spacer)
Including, but not limited to. The fused ring can be optionally substituted and it can be a heterocycle or a carbocycle.

  As is apparent from the above examples, the spacer atoms that produce the desired separation can themselves be part of a group. The group may be, for example, aliphatic, heteroaliphatic, haloaliphatic, heterohaloaliphatic, alicyclic, aryl, arylalkyl, heteroaryl, non-aromatic heterocycle, or substituted alkyl, all of which Can be substituted). Thus, the term “spacer of 1-5 atoms” means a spacer in which two groups are separated by 1, 2, 3, 4 or 5 atoms, which is the group that constitutes the spacer. Does not show the overall size.

には、該生成する環は、Ａ、Ｂ、ＡおよびＢの両方が結合する炭素原子、並びに連結基を含む。特に断らない限り、該連結基はいずれかの鎖長であり得て、そして場合により置換され得る。上記の例について言及する場合には、生成する構造は、式：

などを含むが、これらに限定されない。ある実施態様において、連結して環を形成する該２個の原子は、同じ原子と結合しない。例えば、以下のＡおよびＢが環：

を形成する場合には、生成する環は、Ａ、Ｂ、ＡおよびＢを既に連結した３個の炭素原子、並びに連結基を含む。生成する構造の例は、式：

などを含むが、これらに限定されない。 The term “links to form a ring” means a structure that results when two atoms that are bonded to either one atom or an atom that ultimately binds itself are each bonded to a linking group. Means a situation where a ring forms. The resulting ring contains two atoms, atoms previously linked to these atoms, and a linker. For example, when the following A and B are “linked to form a ring”:

The resulting ring includes A, B, the carbon atom to which both A and B are attached, and the linking group. Unless otherwise indicated, the linking group can be any chain length and can be optionally substituted. When referring to the above example, the resulting structure has the formula:

Including, but not limited to. In certain embodiments, the two atoms that are joined to form a ring are not bonded to the same atom. For example, the following A and B are rings:

The resulting ring contains three carbon atoms already linked to A, B, A and B, and a linking group. An example of a structure to generate is the formula:

Including, but not limited to.

  The substituent “R”, alone and without multiple designations, may be from alkyl, cycloalkyl, aryl, heteroaryl (attached at an endocyclic carbon), or non-aromatic heterocycle (attached at an endocyclic carbon). Means the selected substituent.

  The term “O-carboxy” refers to a group of formula RC (═O) O—.

  The term “C-carboxy” refers to a group of formula —C (═O) OR.

The term “acetyl” refers to a group of formula —C (═O) CH ₃ .

The term “trihalomethanesulfonyl” refers to a group of the formula X ₃ CS (═O) ₂ —, where X is a halogen.

  The term “cyano” refers to a group of formula —CN.

  The term “isocyanate” means a group of formula —NCO.

  The term “thiocyanate” refers to a group of formula —CNS.

  The term “isothiocyanate” refers to a group of formula —NCS.

  The term “sulfonyl” means a group of the formula —S (═O) —R.

The term “S-sulfonamide” refers to a group of formula —S (═O) ₂ NR.

The term “N-sulfonamido” refers to a group of formula RS (═O) ₂ NH—.

The term “trihalomethanesulfonamide” means a group of the formula X ₃ CS (═O) ₂ NR—.

  The term “O-carbamyl” refers to a group of formula —OC (═O) —NR.

  The term “N-carbamyl” refers to a group of formula ROC (═O) —NH—.

  The term “O-thiocarbamyl” refers to a group of formula —OC (═S) —NR.

  The term “N-thiocarbamyl” refers to a group of formula ROC (═S) NH—.

The term “C-amido” refers to a group of formula —C (═O) —NR ₂ .

  The term “N-amido” refers to a group of formula RC (═O) NH—.

The term “ester” refers to the formula — (R) _n —COOR ′ where R and R ′ are independently alkyl, cycloalkyl, aryl, heteroaryl (attached at an endocyclic carbon), or non-aromatic Means a chemical molecule having a family heterocycle (attached at a ring carbon and n is 0 or 1).

The term “amido” refers to the formula — (R) _n —C (O) NHR ′ or — (R) _n —NHC (O) R ′ where R and R ′ are independently alkyl, cycloalkyl , Aryl, heteroaryl (bonded at the ring carbon), or heteroalicyclic (bonded at the ring carbon), and n is 0 or 1. In certain embodiments, the amide can be an amino acid or a peptide.

  The terms “amine”, “hydroxy”, and “carboxyl” include those groups that are esterified or amidated. The recipes and specific groups used to achieve esterification and amidation are known to those skilled in the art and these are cited sources (eg, Greene and Wuts, Protective Groups in Organic Synthesis, 3rd edition). , John Wiley & Sons, New York, NY, 1999 (which is part of this specification).

  Unless otherwise indicated, the term “optionally substituted” means a group in which 0, 1, or more of the hydrogen atoms are replaced with one or more of the following groups. The groups are independently alkyl, heteroalkyl, haloalkyl, heterohaloalkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, non-aromatic heterocycle, hydroxy, alkoxy, aryloxy, mercapto, alkylthio, arylthio, cyano, Halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amide, N-amide, S-sulfonamide, N-sulfonamide, C-carboxy, O-carboxy, isocyanate , Thiocyanate, isothiocyanate, nitro, silyl, trihalomethanesulfonyl, or amino (including, for example, mono- and di-substituted amino groups, and protected derivatives of amino groups). The protecting groups (and protecting groups that can form the protected derivatives) are known to those skilled in the art and can be found in the cited references (eg Greene and Wuts above). In embodiments in which two or more hydrogen atoms are substituted, the substituents can be joined to form a ring.

  The term “carrier” refers to a compound that facilitates the incorporation of another compound into a cell or tissue. For example, dimethyl sulfoxide (DMSO) is a commonly used carrier to improve the uptake of certain organic compounds into cells or tissues.

  The term “pharmaceutical agent” means a chemical compound or composition capable of inducing a desired therapeutic effect in a patient. In certain embodiments, the pharmaceutical agent comprises an active agent, which is an agent that induces a desired therapeutic effect. In certain embodiments, the pharmaceutical agent comprises a prodrug. In certain embodiments, the pharmaceutical agent comprises an inert ingredient (eg, carrier, excipient, etc.).

  The term “pharmaceutical composition” means a pharmaceutical agent combined with one or more inert ingredients (eg, carriers, excipients, etc.) for pharmaceutical administration.

  The term “therapeutically effective amount” means an amount of a pharmaceutical agent or composition sufficient to achieve the desired therapeutic effect.

  The term “prodrug” means a pharmaceutical agent that is converted from a less active form into a corresponding more active form in vivo.

  The term “pharmaceutically acceptable” does not significantly inhibit the biological activity, pharmacological activity, and / or other properties of a compound after it is administered to a patient. It refers to the formulation form of the compound. In certain embodiments, the pharmaceutically acceptable formulation does not cause significant irritation to the patient.

  The term “simultaneous administration” means that one or more pharmaceutical agents are administered to a patient. In certain embodiments, co-administered pharmaceutical agents are administered together in a single dosage unit. In certain embodiments, co-administered pharmaceutical agents are administered separately. In certain embodiments, the co-administered pharmaceutical agents are administered simultaneously. In certain embodiments, co-administered pharmaceutical agents are administered at different times.

  The term “patient” includes human and animal subjects.

  The term “substantially pure” is the dominant species in which the species of interest (eg, compound) is present (ie, more abundant on a molar basis than any other individual species in the composition). It exists). In certain embodiments, the substantially pure fraction is a composition comprising at least about 50% (on a molar basis) of all species in which the species of interest is present. In certain embodiments, a substantially pure composition comprises about 80%, 85%, 90%, 95%, or 99% or more of all species present in the composition. In certain embodiments, the species of interest are purified to essentially homogeneity (contaminating species cannot be detected in the composition by conventional detection methods), where the composition is essentially Including single species.

  The term “tissue-selectivity” refers to a compound that modulates a biological activity in one tissue to a greater or lesser extent than it modulates a biological activity in another tissue. Means ability. The biological activities in different tissues may be the same or they may be different. Biological activity in different tissues can be mediated by the same type of target receptor. For example, in certain embodiments, a tissue-selective compound modulates a receptor-mediated biological activity in one tissue and a receptor-mediated biological in another tissue type. The activity may not be modulated or may be modulated to a lesser extent.

  The term “tracking” means observing an effect or no effect. In certain embodiments, cells are tracked after contacting the cells with a compound of the invention. Examples of effects that can be followed include, but are not limited to, changes in cell phenotype, cell proliferation, receptor activity, or interactions between the receptor and compounds known to bind to the receptor. Not.

  The term “cell phenotype” means a physical or biological property of a cell. Examples of properties that constitute a phenotype include cell size, cell growth, cell differentiation, cell survival, apoptosis (cell death), or utilization of metabolic nutrients (eg, glucose uptake). However, it is not limited to these. Certain changes or absence of changes in the cell phenotype are easily followed using techniques known in the art.

  The term “cell proliferation” means the rate at which cells divide. In certain embodiments, the cell is present in situ in the organism. In certain embodiments, the cells are grown in vitro in a container. The number of cells growing in the container can be quantified by one of ordinary skill in the art (eg, by counting cells in a certain area using a microscope, or of cells in an appropriate medium). By using an experimental device to measure density). A person skilled in the art can calculate cell proliferation by measuring the number of cells two or more times.

  The term “contacting” means that two or more substances are almost close enough that they can interact. In certain embodiments, the contacting can be accomplished in a container (eg, test bowl, petri dish, etc.). In certain embodiments, the contacting can be performed in the presence of additional materials. In certain embodiments, the contacting can be performed in the presence of a cell. In such embodiments, one or more of the contacting materials may be present inside the cell. The cell may be alive or dead. The cells may or may not be intact.

(Compound)
A compound that modulates one or more TPO activities and / or binds to a TPO receptor functions for health. In certain embodiments, the compounds of the invention are useful for treating any of a variety of diseases or conditions.

  In certain embodiments, the present invention provides selective TPO modifiers. In certain embodiments, the present invention provides selective TPO receptor binding agents. In certain embodiments, the present invention provides methods of making and using selective TPO modulators and / or selective TPO receptor binding agents. In certain embodiments, the selective TPO modulator is a TPO receptor agonist, partial agonist, and / or antagonist.

の化合物、またはその医薬的に許容し得る塩、エステル、アミド、もしくはプロドラッグに関する。 In certain embodiments, the present invention provides compounds of formula I, II, or III:

Or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof.

In certain embodiments, R ¹ is selected from hydrogen, CO ₂ R ¹⁰ , CONR ¹⁰ R ¹¹ , SO ₃ R ¹⁰ , or a carboxylic acid bioequivalent. In embodiments where R ¹ is a carboxylic acid bioequivalent, R ¹ is tetrazole, NHSO ₂ R ¹⁵ , OC (S) NR ¹⁰ R ¹¹ , SC (O) NR ¹⁰ R ¹¹ , thiazolidinedione, oxazolidine It is selected from dione or 1-oxa-2,4-diazolidine-3,5-dione.

In certain embodiments, R ² and R ³ are each independently hydrogen, OR ¹² , NR ¹² R ¹³ , optionally substituted C ₁ -C ₄ aliphatic, optionally substituted C ₁ -C ₄ halo. Selected from aliphatic, optionally substituted C ₁ -C ₄ heteroaliphatic, (CH ₂ ) _m R ¹⁴ , optionally substituted ring, or none. In certain such embodiments, R ² and R ³ are each independently an optionally substituted C ₁ -C ₄ alkyl, an optionally substituted C ₁ -C ₄ haloalkyl, or an optionally substituted C _1- Selected from C ₄ heteroalkyl. In certain embodiments, R ² and R ³ are taken together to form an optionally substituted olefin. In certain embodiments, R ² and R ³ are joined to form an optionally substituted C ₃ -C ₈ ring. In certain such embodiments, R ² and R ³ are joined to form an optionally substituted carbocycle, an optionally substituted heterocycle, an optionally substituted aromatic ring, or an optionally substituted non-aromatic ring. Form. In certain such embodiments, R ² and R ³ are linked to optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alicyclic, or optionally substituted non-aromatic. Heterocycle is formed. In certain embodiments, R ² and R ³ are joined to form an optionally substituted aryl or an optionally substituted heteroaryl. In certain embodiments, R ² and R ³ are joined to form an aryl.

In certain embodiments, R ⁴ is hydrogen, F, Cl, Br, optionally substituted C ₁ -C ₄ aliphatic, optionally substituted C ₁ -C ₄ haloaliphatic, optionally substituted C selected from a ring which is substituted by ₁ -C ₄ heteroaliphatic, or. In certain such embodiments, R ⁴ is selected from optionally substituted C ₁ -C ₄ alkyl, optionally substituted C ₁ -C ₄ haloalkyl, or optionally substituted C ₁ -C ₄ heteroalkyl. .

In certain embodiments, R ⁵ is selected from hydrogen, OR ¹⁰ , SR ¹⁰ , NHR ¹¹ , or CO ₂ H.

In certain embodiments, R ⁶ is hydrogen, OR ¹² , NR ¹² R ¹³ , F, Cl, Br, optionally substituted C ₁ -C ₄ aliphatic, optionally substituted C ₁ -C ₄ halofatty. Selected from the group, an optionally substituted C ₁ -C ₄ heteroaliphatic, or an optionally substituted ring. In certain such embodiments, R ⁶ is selected from optionally substituted C ₁ -C ₄ alkyl, optionally substituted C ₁ -C ₄ haloalkyl, or optionally substituted C ₁ -C ₄ heteroalkyl. . In certain embodiments, R ⁶ is selected from an optionally substituted carbocycle, an optionally substituted heterocycle, an optionally substituted aromatic ring, or an optionally substituted non-aromatic ring. In certain such embodiments, R ⁶ is selected from optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alicyclic, or optionally substituted non-aromatic heterocycle. In certain embodiments, R ⁶ is selected from optionally substituted aryl or optionally substituted heteroaryl. In certain embodiments, R ⁶ is selected from optionally substituted aryl. In certain embodiments, R ⁶ is aryl.

In certain embodiments, R ⁷ is hydrogen, optionally substituted C ₁ -C ₈ aliphatic, optionally substituted C ₁ -C ₈ haloaliphatic, optionally substituted C ₁ -C ₈ heterofatty. Selected from the group, an optionally substituted C ₁ -C ₈ heterohaloaliphatic, an optionally substituted ring, or (CH ₂ ) _m R ¹⁴ . In certain such embodiments, R ⁷ is optionally substituted C ₁ -C ₈ alkyl, optionally substituted C ₁ -C ₈ haloalkyl, optionally substituted C ₁ -C ₈ heteroalkyl, or optionally. Selected from substituted C ₁ -C ₈ heterohaloalkyl. In certain embodiments, R ⁷ is selected from an optionally substituted carbocycle, an optionally substituted heterocycle, an optionally substituted aromatic ring, or an optionally substituted non-aromatic ring. In certain such embodiments, R ⁷ is selected from optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alicyclic, or optionally substituted non-aromatic heterocycle. In certain embodiments, R ⁷ is selected from optionally substituted aryl or optionally substituted heteroaryl. In certain embodiments, R ⁷ is selected from optionally substituted aryl. In certain such embodiments, R ⁷ is selected from an aryl ring optionally fused to one or more additional rings. In certain embodiments, R ⁷ is aryl. In certain embodiments, R ⁷ is an optionally substituted phenyl ring.

In certain embodiments, R ⁸ and R ⁹ are each independently hydrogen, F, Cl, Br, optionally substituted C ₁ -C ₄ aliphatic, optionally substituted C ₁ -C ₄ haloaliphatic. , Optionally substituted C ₁ -C ₄ heteroaliphatic, optionally substituted C ₁ -C ₄ heterohaloaliphatic, or optionally substituted rings. In certain such embodiments, R ⁸ and / or R ⁹ are independently optionally substituted C ₁ -C ₄ alkyl, optionally substituted C ₁ -C ₄ haloalkyl, optionally substituted C _1- Selected from C ₄ heteroalkyl, or optionally substituted C ₁ -C ₄ heterohaloalkyl. In certain embodiments, R ⁸ and / or R ⁹ are selected from an optionally substituted carbocycle, an optionally substituted heterocycle, an optionally substituted aromatic ring, or an optionally substituted non-aromatic ring. . In certain such embodiments, R ⁸ and / or R ⁹ are optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alicyclic, or optionally substituted non-aromatic hetero. Selected from the ring. In certain embodiments, R ⁸ and / or R ⁹ are selected from optionally substituted aryl or optionally substituted heteroaryl. In certain embodiments, R ⁸ and / or R ⁹ are selected from optionally substituted aryl. In certain embodiments, R ⁸ and / or R ⁹ is aryl.

In certain embodiments, R ¹⁰ is hydrogen, optionally substituted C ₁ -C ₄ aliphatic, optionally substituted C ₁ -C ₄ haloaliphatic, optionally substituted C ₁ -C ₄ heterofatty. group, when selected from a ring optionally substituted by C ₁ -C ₄ Heteroharo aliphatic or substituted by. In certain such embodiments, R ¹⁰ is optionally substituted C ₁ -C ₄ alkyl, optionally substituted C ₁ -C ₄ haloalkyl, optionally substituted C ₁ -C ₄ heteroalkyl, or optionally. Selected from substituted C ₁ -C ₄ heterohaloalkyl. In certain embodiments, R ¹⁰ is selected from an optionally substituted ring. In certain such embodiments, R ¹⁰ is selected from an optionally substituted carbocycle, an optionally substituted heterocycle, an optionally substituted aromatic ring, or an optionally substituted non-aromatic ring. In certain such embodiments, R ¹⁰ is selected from optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alicyclic, or optionally substituted non-aromatic heterocycle. In certain embodiments, R ¹⁰ is selected from optionally substituted aryl or optionally substituted heteroaryl. In certain embodiments, R ¹⁰ is selected from optionally substituted aryl. In certain embodiments, R ¹⁰ is aryl.

In certain embodiments, R ¹¹ is hydrogen, SO ₂ R ¹⁵ , optionally substituted C ₁ -C ₄ aliphatic, optionally substituted C ₁ -C ₄ haloaliphatic, optionally substituted C _1. -C ₄ heteroaliphatic, if chosen from rings that are optionally substituted by C ₁ -C ₄ Heteroharo aliphatic or substituted by. In certain such embodiments, R ¹¹ is optionally substituted C ₁ -C ₄ alkyl, optionally substituted C ₁ -C ₄ haloalkyl, optionally substituted C ₁ -C ₄ heteroalkyl, or optionally. Selected from substituted C ₁ -C ₄ heterohaloalkyl. In certain embodiments, R ¹¹ is selected from an optionally substituted ring. In certain such embodiments, R ¹¹ is selected from an optionally substituted carbocycle, an optionally substituted heterocycle, an optionally substituted aromatic ring, or an optionally substituted non-aromatic ring. In certain such embodiments, R ¹¹ is selected from optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alicyclic, or optionally substituted non-aromatic heterocycle. In certain embodiments, R ¹¹ is selected from optionally substituted aryl or optionally substituted heteroaryl. In certain embodiments, R ¹¹ is selected from optionally substituted aryl. In certain embodiments, R ¹¹ is aryl.

In certain embodiments, R ¹² and R ¹³ are each independently hydrogen, optionally substituted C ₁ -C ₄ aliphatic, optionally substituted C ₁ -C ₄ haloaliphatic, optionally substituted. Selected from C ₁ -C ₄ heteroaliphatic, optionally substituted C ₁ -C ₄ heterohaloaliphatic, optionally substituted ring, or (CH ₂ ) _m R ¹⁴ . In certain such embodiments, R ¹² and / or R ¹³ are independently optionally substituted C ₁ -C ₄ alkyl, optionally substituted C ₁ -C ₄ haloalkyl, optionally substituted C _1- Selected from C ₄ heteroalkyl, or optionally substituted C ₁ -C ₄ heterohaloalkyl. In certain embodiments, R ¹² and / or R ¹³ is selected from an optionally substituted carbocycle, an optionally substituted heterocycle, an optionally substituted aromatic ring, or an optionally substituted non-aromatic ring. . In certain such embodiments, R ¹² and / or R ¹³ are optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alicyclic, or optionally substituted non-aromatic hetero. Selected from the ring. In certain embodiments, R ¹² and / or R ¹³ is selected from optionally substituted aryl or optionally substituted heteroaryl. In certain embodiments, R ¹² and / or R ¹³ is selected from optionally substituted aryl. In certain embodiments, R ¹² and / or R ¹³ is aryl. In certain embodiments, one of R ¹² or R ¹³ is a ring and the other of R ¹² and R ¹³ is hydrogen.

In certain embodiments, R ¹² and R ¹³ are joined to form an optionally substituted C ₂ -C ₈ heterocycle. In certain embodiments, R ¹² and R ¹³ are joined to form an optionally substituted C ₂ -C ₈ heteroaryl. In certain embodiments, R ¹² and R ¹³ are joined to form an optionally substituted C ₂ -C ₈ non-aromatic heterocycle.

In certain embodiments, R ¹⁴ is selected from an optionally substituted ring. In certain such embodiments, R ¹⁴ is selected from an optionally substituted carbocycle, an optionally substituted heterocycle, an optionally substituted aromatic ring, or an optionally substituted non-aromatic ring. In certain such embodiments, R ¹⁴ is selected from optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alicyclic, or optionally substituted non-aromatic heterocycle. In certain embodiments, R ¹⁴ is selected from optionally substituted aryl or optionally substituted heteroaryl. In certain embodiments, R ¹⁴ is selected from optionally substituted aryl. In certain embodiments, R ¹⁴ is aryl.

In certain embodiments, R ¹⁵ is selected from hydrogen, optionally substituted C ₁ -C ₃ aliphatic, optionally substituted C ₁ -C ₃ haloaliphatic, or optionally substituted ring. In certain such embodiments, R ¹⁵ is selected from optionally substituted C ₁ -C ₃ alkyl or optionally substituted C ₁ -C ₃ haloalkyl. In certain embodiments, R ¹⁵ is optionally substituted aryl. In certain embodiments, R ¹⁵ is selected from alkyl, haloalkyl, alicyclic, or aryl. In certain embodiments, R ¹⁵ is selected from an optionally substituted ring. In certain such embodiments, R ¹⁵ is selected from an optionally substituted carbocycle, an optionally substituted heterocycle, an optionally substituted aromatic ring, or an optionally substituted non-aromatic ring. In certain such embodiments, R ¹⁵ is selected from optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alicyclic, or optionally substituted non-aromatic heterocycle. In certain embodiments, R ¹⁵ is selected from optionally substituted aryl or optionally substituted heteroaryl. In certain embodiments, R ¹⁵ is selected from optionally substituted aryl. In certain embodiments, R ¹⁵ is aryl.

In certain embodiments, Y is a spacer having 1, 2, 3, 4, 5, 7, or 8 atoms. In certain embodiments, Y is a 1-4 atom spacer selected from optionally substituted C ₁ -C ₆ aliphatic or optionally substituted C ₁ -C ₆ heteroaliphatic. In certain such embodiments, Y is optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, optionally substituted C ₂ -C ₆ alkenyl, or optionally substituted. Is a spacer having 1 to 4 atoms selected from C ₂ -C ₆ heteroalkenyl.

In certain embodiments, Y is a 1 to 4 atom spacer containing a ring. In such embodiments, Y is optionally substituted phenyl, optionally substituted monocyclic heteroaryl, optionally substituted C ₃ -C ₅ heterocycle, or optionally substituted alicyclic (eg, Including, but not limited to, optionally substituted cycloalkyl and optionally substituted cycloalkenyl.

In certain embodiments, Y is (1) an optionally substituted phenyl, an optionally substituted monocyclic heteroaryl, an optionally substituted C ₃ -C ₅ heterocycle, or an optionally substituted alicycle. Both a ring selected from the formula and (2) a substituted C ₁ -C ₆ aliphatic, or optionally substituted C ₁ -C ₆ heteroaliphatic spacer of 1-4 atoms. It is a spacer having 2 to 6 atoms.

ではあり得ない。 In certain embodiments, Y is not —N═CR ⁶ oriented to form dihydropyrazole. Thus, in this embodiment, the ring comprising Y has the formula:

It can't be.

から選ばれる。 In some embodiments, Y is of the formula:

Chosen from.

  In certain embodiments, Q is selected from O or S.

In certain embodiments, X is selected from O, S, NR ¹⁰ , or CR ¹⁰ R ¹⁰ .

In certain embodiments, Z is a 1-5 spacer. In certain embodiments, Z is optionally a 2-5 atoms spacer selected from _C 1 -C ₈ heteroaryl, which are optionally substituted by a _C 6 _{-C 10} aryl or substituted. In certain embodiments, Z is optionally substituted C ₁ -C ₆ alkyl, optionally substituted C ₁ -C ₆ heteroalkyl, optionally substituted C ₁ -C ₆ haloalkyl, optionally substituted. C ₂ -C ₆ alkenyl, when _C 2 -C ₆ heteroalkenyl substituted by, is optionally substituted substituted _C 2 -C ₆ haloalkenyl, optionally substituted _C 2 -C ₆ alkynyl, or optionally, And a spacer having 1 to 5 atoms selected from C _{2 to} C ₆ heteroalkyl.

  In certain embodiments, m is 0, 1, or 2.

In certain embodiments, n is 0 or 1. In embodiments where n is 0, optionally R ¹ is directly linked to Z and R ² and / or R ^{3 is} none. For example, when Z is a phenyl ring and n is 0, R ¹ is directly linked to the phenyl ring and both R ² and R ³ are absent.

In embodiments where two or more specific groups are present, the identity of the two or more specific groups is independently selected, and therefore they may be the same or different from one another. For example, the compounds of the present invention contain two or more R ¹⁴ groups. The identity of the two or more R ¹⁴ groups is independently selected. Thus, in certain embodiments, all of the R ¹⁴ groups are the same as each other; in certain embodiments, all of the R ¹⁴ groups are different from each other; in some embodiments, some of the R ¹⁴ groups are the same as each other; And some are different from each other. This independent selection applies one or more times to any group present in the compound.

One skilled in the art can narrow the complete list of possible identities (all R groups, Y, Q, Z, m, and n) for each of the groups exemplified above to It will be appreciated that a short list can be provided. For example, because each of the possible identities is included in a longer list of possible identities, in certain embodiments, R ¹ is hydrogen, CO ₂ R ¹⁰ , CONR ¹⁰ R ¹¹ , SO ₃ R ¹⁰ , or carvone. It should be understood that in some embodiments, R ¹ may be selected from CO ₂ R ¹⁰ , CONR ¹⁰ R ¹¹ , or SO ₃ R ¹⁰ , as selected from acid biological equivalents. Those skilled in the art will also recognize that broader terms include narrower term combinations (which can be substituted and selected). For example, in certain embodiments, R ² is selected from optionally substituted C ₁ -C ₄ aliphatic. Since aliphatic includes, but is not limited to alkyl and alkylene, in certain embodiments, R ² is selected from optionally substituted C ₁ -C ₄ alkyl or optionally substituted C ₁ -C ₄ alkenyl. Can be. Similarly, in certain embodiments, alkyl and alkenyl are included in the definition of C ₁ -C ₄ aliphatic, so that R ² is optionally substituted C ₂ -C ₃ alkyl or optionally substituted C _2- selected from the group consisting of C ₄ alkenyl.

One skilled in the art will also understand that the above groups can be selected in any combination. For example, in certain embodiments, R ¹ is selected from hydrogen, CO ₂ R ¹⁰ , CONR ¹⁰ R ¹¹ , SO ₃ R ¹⁰ , or a carboxylic acid biological equivalent; R ² is hydrogen, OR ¹² , NR ¹² R ¹³ , optionally substituted C ₁ -C ₄ aliphatic, optionally substituted C ₁ -C ₄ haloaliphatic, optionally substituted C ₁ -C ₄ heteroaliphatic, (CH ₂ ) _m R ¹⁴ is selected from an optionally substituted ring or none. Thus, in certain embodiments, R ¹ can be selected from hydrogen or CO ₂ R ¹⁰ ; at the same time, since the list of possible identities is included in the list of possible identities above, R ² is , Hydrogen, OR ¹² , NR ¹² R ¹³ , or optionally substituted C ₁ -C ₄ aliphatic. The selection of the combination includes all groups herein.

  In certain embodiments, the compound of formula I, II, or III is a selective TPO modifier. In certain embodiments, the compound of formula I, II, or III is a selective TPO receptor agonist. In certain embodiments, the compound of formula I, II, or III is a selective TPO receptor antagonist. In certain embodiments, the compound of formula I, II, or III is a selective TPO receptor partial agonist. In certain embodiments, the compound of formula I, II, or III is a tissue-specific selective TPO modulator. In certain embodiments, the compound of formula I, II, or III is a selective TPO receptor binding compound. In certain embodiments, the compound of formula I, II, or III is a TPO mimetic.

In certain embodiments, the present invention provides the following compound:
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carbon Acid (compound 101);
2'-hydroxy-3 '-{N'-[2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3-carboxylic acid ( Compound 102);
2'-hydroxy-3 '-{N'-[2-oxo-1- (4-ethyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3-carboxylic acid ( Compound 103);
2'-hydroxy-3 '-{N'-[2-oxo-1- (4-trifluoromethoxy-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3-carboxylic Acid (compound 104);
3 '-{N'-[1- (3-Fluoro-4-methoxy-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -Carboxylic acid (compound 105);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-4-carboxyl An acid (compound 106);
2'-hydroxy-3 '-{N'-[2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-4-carboxylic acid ( Compound 107);
2'-hydroxy-3 '-{N'-[2-oxo-1- (4-ethyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-4-carboxylic acid ( Compound 108);
3 '-{N'-[1- (4-tert-Butyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic Acid (compound 109);
2'-hydroxy-3 '-{N'-[2-oxo-1- (4-trifluoromethyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3-carboxylic Acid (compound 110);
3 ′-[N ′-(1-Benzyl-5-chloro-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2′-hydroxy-biphenyl-3-carboxylic acid (compound 111 );
3 ′-[N ′-(1-Benzyl-5-methyl-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2′-hydroxy-biphenyl-3-carboxylic acid (compound 112 );
3 ′-[N ′-(1-benzyl-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2′-hydroxy-biphenyl-3-carboxylic acid (compound 113);
2'-hydroxy-3 '-{N'-[2-oxo-1- (4-trifluoromethylphenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-4-carboxylic acid (Compound 114);
3 '-{N'-[1- (3,4-dichloro-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic Acid (compound 115);
2'-hydroxy-3 '-{N'-[1- (4-methyl-3-trifluoromethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl -3-carboxylic acid (compound 116);
3 '-{N'-[1- (3-Fluoro-4-trifluoromethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 117);
3 '-{N'-[1- (3,5-bis-trifluoromethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 118);
3 ′-{N ′-[3- (3,4-dimethyl-phenyl) -4-oxo-2-thioxo-thiazolidine-5-ylidene] -hydrazino} -2′-hydroxy-biphenyl-3-carboxylic acid ( Compound 119);
2'-hydroxy-3 '-{N'-[1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3-carboxylic acid ( Compound 120);
3 '-{N'-[1- (2-Fluoro-4-trifluoromethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (Compound 121);
3 '-{N'-[1- (2-Fluoro-4-methyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -Carboxylic acid (compound 122);
3 '-{N'-[1- (4-Chloro-3-trifluoromethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (Compound 123);
3 '-{N'-[1- (4-Butyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid ( Compound 124);
3 '-{N'-[1- (3-Fluoro-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid ( Compound 125);
2'-hydroxy-3 '-[N'-(2-oxo-1-m-tolyl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid (Compound 126);
3 '-{N'-[1- (4-Fluoro-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid ( Compound 127);
3 ′-[N ′-(1-Benzyl-5-methoxy-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2′-hydroxy-biphenyl-3-carboxylic acid (compound 128 );
2'-hydroxy-3 '-{N'-[2-oxo-1- (3-trifluoromethyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3-carboxylic Acid (compound 129);
3 '-{N'-[5-Chloro-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -Carboxylic acid (compound 130);
3 '-{N'-[6-Chloro-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -Carboxylic acid (compound 131);
3 '-{N'-[5-Fluoro-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -Carboxylic acid (compound 132);
3 '-{N'-[5-methoxy-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -Carboxylic acid (compound 133);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -5-fluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 134);
3 '-{N'-[1- (4-Fluoro-3-trifluoromethyl-phenyl) -5-fluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid (compound 135);
3 '-{N'-[1- (3,5-dichloro-phenyl) -5-fluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 136);
3 '-{N'-[1- (4-propyl-phenyl) -6-chloro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -Carboxylic acid (compound 137),
And any pharmaceutically acceptable salt, ester, amide, or prodrug of any of the compounds. In certain embodiments, the compound is a selective TPO modifier.

In certain embodiments, the present invention provides the following compound:
(±) -2'-hydroxy-3 '-(N'-{2-oxo-1- [4- (2,2,2-trifluoro-1-hydroxy-ethyl) -phenyl] -1,2- Dihydro-indole-3-ylidene} -hydrazino) -biphenyl-3-carboxylic acid (compound 138);
(±) -2'-hydroxy-3 '-(N'-{2-oxo-1- [4- (2,2,2-trifluoro-1-methoxy-ethyl) -phenyl] -1,2- Dihydro-indole-3-ylidene} -hydrazino) -biphenyl-3-carboxylic acid (compound 139);
2'-hydroxy-3 '-(N'-{2-oxo-1- [4- (2,2,2-trifluoro-ethyl) -phenyl] -1,2-dihydro-indole-3-ylidene} -Hydrazino) -biphenyl-3-carboxylic acid (compound 140);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -4,5-dimethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid (compound 141);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -5-fluoro-4-methyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid (compound 142);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -5-fluoro-6-methyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid (compound 143);
5- (4- {N '-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] -hydrazino} -3-hydroxy -Benzylidene) -thiazolidine-2,4-dione (compound 144);
5- (4- {N '-[1- (3,4-dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -3-hydroxy-benzylidene) -thiazolidine -2,4-dione (compound 145);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 146);
3 '-{N'-[4-Chloro-1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 147);
5- (4- {N '-[1- (3,4-Dimethyl-phenyl) -4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino } -3-hydroxy-benzylidene) -thiazolidine-2,4-dione (compound 148);
5- (4- {N '-[4-Chloro-1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino } -3-hydroxy-benzylidene) -thiazolidine-2,4-dione (compound 149);
3- (4- {N '-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -3- Hydroxy-phenyl) -acrylic acid (compound 150);
1- (3,4-dimethyl-phenyl) -3-{[2-hydroxy-4- (4-oxo-2-thioxo-thiazolidine-5-ylidenemethyl) -phenyl] -hydrazono} -6-trifluoromethyl- 1,3-dihydro-indol-2-one (compound 151);
1- (3,4-dimethyl-phenyl) -4-fluoro-3-{[2-hydroxy-4- (4-oxo-2-thioxo-thiazolidine-5-ylidenemethyl) -phenyl] -hydrazono} -6- Trifluoromethyl-1,3-dihydro-indol-2-one (compound 152);
5- (3- {N '-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2- Hydroxy-benzylidene) -thiazolidine-2,4-dione (compound 153);
3 '-{N'-[5-Chloro-2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -Carboxylic acid (compound 154);
2'-hydroxy-3 '-{N'-[1- (4-methylsulfanyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3-carboxylic acid (Compound 155);
2'-hydroxy-3 '-{N'-[1- (4-methoxymethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3-carboxylic acid (Compound 156);
(±) -2'-hydroxy-3 '-(N'-{2-oxo-1- [4- (2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl) -phenyl]- 1,2-dihydro-indole-3-ylidene} -hydrazino) -biphenyl-3-carboxylic acid (compound 157);
3 '-{N'-[5-Fluoro-1- (4-methyl-3-trifluoromethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid (compound 158);
2'-hydroxy-3 '-(N'-{2-oxo-1- [4- (2,2,2-trifluoro-1-methoxy-1-methyl-ethyl) -phenyl] -1,2- Dihydro-indole-3-ylidene} -hydrazino) -biphenyl-3-carboxylic acid (compound 159);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -6-fluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 160);
3 '-{N'-[6-Fluoro-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -Carboxylic acid (compound 161);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-5-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid (compound 162);
3 '-{N'-[6-Fluoro-2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -Carboxylic acid (compound 163);
2'-hydroxy-3 '-{N'-[2-oxo-1- (4-propyl-phenyl) -5-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl -3-carboxylic acid (compound 164);
3 '-{N'-[4,5-Difluoro-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 165);
2′-Hydroxy-3 ′-[N ′-(2-oxo-1-piperidin-4-yl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid (Compound 166 );
3 '-{N'-[5-Fluoro-1- (2-fluoro-4-methyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid (compound 167);
2'-hydroxy-3 '-[N'-(1-methyl-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid (Compound 168);
3 ′-[N ′-(1-cyclopentyl-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2′-hydroxy-biphenyl-3-carboxylic acid (Compound 169);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -6-methyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 170);
2'-hydroxy-3 '-[N'-(2-oxo-1-phenyl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid (Compound 171);
3 '-[N'-(6-Fluoro-2-oxo-1-phenyl-2,3-dihydro-1H-indol-3-yl) -hydrazino] -2'-hydroxy-biphenyl-3-carboxylic acid ( Compound 172);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -6-isopropyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 173);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -4-isopropyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 174);
3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -4-fluoro- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 175);
5'-Chloro-3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -4-fluoro-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 176);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -6-fluoro- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 177);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -4,5-difluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid (compound 178);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] -hydrazino} -2'-hydroxy- 3-methyl-biphenyl-4-carboxylic acid (compound 179);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-2,3-dihydro-1H-indol-3-yl] -hydrazino} -2- Fluoro-2'-hydroxy-biphenyl-4-carboxylic acid (compound 180);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -4-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-1H-indol-3-yl] -hydrazino } -4-Fluoro-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 181);
5'-Chloro-3 '-{N'-[1- (3,4-dimethyl-phenyl) -4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene ] -Hydrazino} -4-fluoro-2'-hydroxy-biphenyl-3-carboxylic acid (compound 182);
3-[(3'-Carboxy-2-hydroxy-biphenyl-3-yl) -hydrazono] -1- (3,5-dimethyl-phenyl) -2-oxo-2,3-dihydro-1H-indole-6 -Carboxylic acid methyl ester (compound 183);
3-[(3'-carboxy-4'-fluoro-2-hydroxy-biphenyl-3-yl) -hydrazono] -1- (3,5-dimethyl-phenyl) -2-oxo-2,3-dihydro- 1H-indole-6-carboxylic acid methyl ester (compound 184);
3-[(3'-Carboxy-4'-fluoro-2-hydroxy-biphenyl-3-yl) -hydrazono] -1- (3,4-dimethyl-phenyl) -2-oxo-2,3-dihydro- 1H-indole-6-carboxylic acid methyl ester (compound 185);
3-[(3′-carboxy-5-chloro-4′-fluoro-2-hydroxy-biphenyl-3-yl) -hydrazono] -1- (3,5-dimethyl-phenyl) -2-oxo-2, 3-dihydro-1H-indole-6-carboxylic acid methyl ester (compound 186);
3 '-{N'-[1- (2-Cyano-thiophen-3-yl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -Carboxylic acid (compound 187);
2′-Hydroxy-3 ′-[N ′-(2-oxo-1-thiophen-3-yl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid (Compound 188 );
3-[(3'-Carboxy-2-hydroxy-biphenyl-3-yl) -hydrazono] -1- (3,4-dimethyl-phenyl) -2-oxo-2,3-dihydro-1H-indole-6 -Carboxylic acid methyl ester (compound 189);
3 '-{N'-[1- (4-Chloro-3-trifluoromethyl-phenyl) -6-cyano-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid (compound 190);
5'-Chloro-3 '-{N'-[6-cyano-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -4-fluoro -2'-hydroxy-biphenyl-3-carboxylic acid (compound 191);
3 '-{N'-[6-Cyano-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -4-fluoro-2'-hydroxy -Biphenyl-3-carboxylic acid (compound 192);
(±) -1- (3,4-Dimethyl-phenyl) -3-{[2-hydroxy-3 '-(2,2,2-trifluoro-1-hydroxy-ethyl) -biphenyl-3-yl] -Hydrazono} -6-methanesulfonyl-1,3-dihydro-indol-2-one (compound 193);
3 '-{N'-[6-Cyano-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -Carboxylic acid (compound 194);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -5-nitro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 195);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -6-methanesulfonyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy- Biphenyl-3-carboxylic acid (compound 196);
3 '-{N'-[6-Cyano-1- (3,4-dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (Compound 197);
3 '-{N'-[1- (5-Cyano-pyridin-3-yl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -Carboxylic acid (compound 198);
3 ′-[N ′-(1-furan-3-yl-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2′-hydroxy-biphenyl-3-carboxylic acid (Compound 199 );
3 '-[N'-(1-Benzo [1,3] dioxol-5-yl-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2'-hydroxy-biphenyl-3 -Carboxylic acid (compound 200);
2'-hydroxy-3 '-{N'-[1- (3-methyl-thiophen-2-yl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3 -Carboxylic acid (compound 201);
2′-hydroxy-3 ′-[N ′-(2-oxo-1-thiophen-2-yl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid (compound 202 );
2'-hydroxy-3 '-{N'-[1- (4-isopropyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl -3-carboxylic acid (compound 203);
2'-hydroxy-3 '-{N'-[2-oxo-1- (4-propyl-phenyl) -6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl -3-carboxylic acid (compound 204);
3 '-{N'-[1- (4-Ethyl-phenyl) -5,7-difluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 205);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -5,7-difluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid (compound 206);
3 '-{N'-[5,7-Difluoro-2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 207);
3 '-{N'-[5,7-Difluoro-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 208);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid (compound 209);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -6-ethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 210);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -6-methoxy-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 211);
3 '-{N'-[5-Chloro-1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 212);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -6,7-dimethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid (compound 213);
2- (3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 '-Hydroxy-biphenyl-4-yl) -2-methyl-propionic acid (Compound 214);
(-)-2- (3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene]- Hydrazino} -2'-hydroxy-biphenyl-4-yl) -propionic acid (compound 215) and (+)-2- (3 '-{N'-[1- (3,4-dimethyl-phenyl) -2 -Oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-4-yl) -propionic acid (compound 215a);
(±)-(3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-5'-methyl-biphenyl-4-yl) -propionic acid (compound 216);
(±) -2- (3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene]- Hydrazino} -5'-fluoro-2'-hydroxy-biphenyl-4-yl) -propionic acid (compound 217);
5- (4- {N '-[1- (3,4-Dimethyl-phenyl) -5,7-difluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -3- Hydroxy-benzylidene) -thiazolidine-2,4-dione (compound 218);
5- (4- {N '-[1- (4-Ethyl-phenyl) -5,7-difluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -3-hydroxy- Benzylidene) -thiazolidine-2,4-dione (compound 219);
5- (4- {N '-[5,7-Difluoro-2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -3-hydroxy- Benzylidene) -thiazolidine-2,4-dione (compound 220);
5- (3-Hydroxy-4- {N '-[1- (4-isopropyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- Benzylidene) -thiazolidine-2,4-dione (compound 221);
5- (3-hydroxy-4- {N '-[1- (4-isopropyl-phenyl) -2-oxo-5,7-difluoro-1,2-dihydro-indole-3-ylidene] -hydrazino}- Benzylidene) -thiazolidine-2,4-dione (compound 222);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -5'-fluoro -2'-hydroxy-biphenyl-3-carboxylic acid (compound 223);
5'-Chloro-3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (compound 224);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -5'-methyl-biphenyl-3-carboxylic acid (Compound 225);
2'-hydroxy-3 '-{N'-[2-oxo-6-trifluoromethyl-1- (4-trifluoromethyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -Biphenyl-3-carboxylic acid (compound 226);
3 '-{N'-[1- (4-Ethyl-3-methyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid (compound 227);
3 '-{N'-[1- (4-Chloro-3-trifluoromethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 228);
3 '-{N'-[1- (3,5-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -5'-fluoro -2'-hydroxy-biphenyl-3-carboxylic acid (compound 229);
3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -4,5 '-Difluoro-2'-hydroxy-biphenyl-3-carboxylic acid (compound 230);
3 '-{N'-[1- (3,5-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -4,5 '-Difluoro-2'-hydroxy-biphenyl-3-carboxylic acid (compound 231);
4,5'-difluoro-2'-hydroxy-3 '-{N'-[2-oxo-6-trifluoromethyl-1- (4-trifluoromethyl-phenyl) -1,2-dihydro-indole- 3-ylidene] -hydrazino} -biphenyl-3-carboxylic acid (Compound 232);
3 '-{N'-[1- (4-Fluoro-3,5-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 233);
2'-hydroxy-3 '-{N'-[1- (4-methoxy-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl -3-carboxylic acid (compound 234);
3 '-{N'-[1- (4-Fluoro-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 235);
3 '-{N'-[1- (3,5-dimethoxyphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy- Biphenyl-3-carboxylic acid (compound 236);
3 '-{N'-[1- (3,4-dimethoxyphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy- Biphenyl-3-carboxylic acid (compound 237);
3 '-{N'-[1- (3,5-difluorophenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy- Biphenyl-3-carboxylic acid (compound 238);
5'-fluoro-3 '-{N'-[1- (4-fluoro-3,5-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene ] -Hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (compound 239);
4,5'-difluoro-3 '-{N'-[1- (4-fluoro-3,5-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3 -Ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (compound 240);
2'-hydroxy-3 '-{N'-[1- (4-methoxy-3,5-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene ] -Hydrazino} -biphenyl-3-carboxylic acid (compound 241);
2'-hydroxy-3 '-{N'-[1- (4-hydroxy-3,5-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene ] -Hydrazino} -biphenyl-3-carboxylic acid (compound 242);
3 '-{N'-[1- (4-cyclohexyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid ( Compound 243);
2′-Hydroxy-3 ′-[N ′-(2-oxo-1-pyridin-2-yl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid (Compound 244 );
2′-Hydroxy-3 ′-[N ′-(2-oxo-1-pyridin-3-yl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid (Compound 245 );
3 '-{N'-[1- (4-Ethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 246);
3 '-{N'-[1- (4-Ethyl-phenyl) -4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid (compound 247);
3-[(3'-Carboxy-2-hydroxy-biphenyl-3-yl) -hydrazono] -1- (3,5-dimethyl-phenyl) -2-oxo-2,3-dihydro-1-H-indole -5-carboxylic acid methyl ester (compound 248);
3 '-{N'-[1- (3-Chloro-4-methyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid (compound 249);
5- (4- {N '-[1- (3,5-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -3- Hydroxy-benzylidene) -thiazolidine-2,4-dione (compound 250);
2'-hydroxy-3 '-(N'-{2-oxo-1- [4- (4,4,4-trifluorobutyl) -phenyl] -1,2-dihydro-indole-3-ylidene}- Hydrazino) -biphenyl-3-carboxylic acid (compound 251);
3 '-{N'-[1- (3,5-Dimethyl-phenyl) -4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 252);
3 '-{N'-[1- (4-tert-butyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid (compound 253);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-4-carboxylic acid (compound 254);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-bromo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 255);
3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -3-fluoro- 2'-hydroxy-biphenyl-4-carboxylic acid (Compound 256);
3 '-{N'-[1- (3,5-bis-trifluoromethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 '-Hydroxy-biphenyl-3-carboxylic acid (compound 257);
3 '-{N'-[1- (3,4-dichloro-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid (compound 258);
3 '-{N'-[1- (3,5-dichloro-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid (compound 259);
3- (4- {N '-[1- (3,5-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -3- Hydroxy-phenyl) -2-methyl-acrylic acid (compound 260);
3- (4- {N '-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -3- Hydroxy-phenyl) -2-methyl-acrylic acid (compound 261);
2'-hydroxy-3 '-[N'-(2-oxo-7-phenyl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid (Compound 262);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethoxy-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid (compound 263);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6- (1,1,2,2-tetrafluoroethoxy) -1,2-dihydro-indole-3- Ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (compound 264);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -5-methyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 265);
3 '-{N'-[1- (4-Isopropylphenyl) -5-methyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3- Carboxylic acid (compound 266);
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -6-phenyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 267);
3 '-{N'-[1- (3-trifluoromethyl-phenyl) -6-trifluoromethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid (compound 268);
3 '-{N'-[1- (4-trifluoromethoxy-phenyl) -5-trifluoromethoxy-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid (compound 269);
3 '-{N'-[1- (3,5-Dimethyl-phenyl) -6-trifluoromethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid (compound 270);
3 '-{N'-[1- (3-trifluoromethyl-phenyl) -4,6-dimethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid (compound 271);
3 '-{N'-[1- (3-trifluoromethyl-phenyl) -5,6-dimethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid (compound 272);
3 '-{N'-[1- (3,5-Dimethyl-phenyl) -6-trifluoromethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -5′-chloro-4-fluoro-biphenyl-3-carboxylic acid (Compound 273);
3 '-{N'-[1- (3,5-Dimethyl-phenyl) -6-trifluoromethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -4-fluoro-biphenyl-3-carboxylic acid (Compound 274);
3 '-{N'-[6-Chloro-1- (3,4-dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 275);
3 '-{N'-[5-Fluoro-2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -Carboxylic acid (compound 276);
3 '-{N'-[5-Cyano-1- (3,4-dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 277);
3 '-{N'-[6-Chloro-1- (3,5-dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (compound 278);
4-Fluoro-3 '-{N'-[1- (3-fluoro-4-methyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino } -2'-hydroxy-biphenyl-3-carboxylic acid (compound 279),
And any pharmaceutically acceptable salt, ester, amide or prodrug of any of the compounds.

In certain embodiments, the present invention provides the following compound:
3 '-{N'-[1- (4-Chloro-3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid (compound 280);
3 '-{N'-[1- (3,5-Dimethylphenyl) -4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] hydrazino} -2 ' -Hydroxybiphenyl-4-fluoro-3-carboxylic acid (compound 281);
3 '-{N'-[1-Benzo [1,3] dioxol-5-yl-2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] hydrazino} -2'- Hydroxybiphenyl-3-carboxylic acid (compound 282);
3 '-{N'-[1-Benzo [1,3] dioxol-5-yl-2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] hydrazino} -2'- Hydroxybiphenyl-2-fluoro-3-carboxylic acid (compound 283);
3 '-{N'-[1- (3,5-Dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] hydrazino} -2'-hydroxybiphenyl- 2-hydroxy-3-carboxylic acid (compound 284);
3 '-{N'-[1- (3-methoxycarbonylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -2'-hydroxybiphenyl-3- Carboxylic acid (compound 285);
3 ′-{N ′-[1- (3-methoxycarbonylphenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] hydrazino} -2′-hydroxybiphenyl-3-carboxylic acid (compound 286 );
3 '-{N'-[7-aza-1- (3,4-dimethylphenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] hydrazino} -2'-hydroxybiphenyl-3- Carboxylic acid (compound 287);
3 '-{N'-[1- (3,5-Dimethylphenyl) -2-oxo-1,2-dihydro-indole-6-trifluoromethyl-3-ylidene] hydrazino} -2'-hydroxybiphenyl- 3- (2-methyl-2-propionic acid) (Compound 288);
3 '-{N'-[1,3-N, N-dimethylbarbitur-5-ylidene] hydrazino} -2'-hydroxybiphenyl-3-carboxylic acid (Compound 289);
3 '-{N'-[1-N- (4-trifluoromethylbenzyl) -2,8-dioxo-1,2,7,8-tetrahydroisoquinoline-7-ylidene] hydrazino} -2'-hydroxybiphenyl -3-carboxylic acid (compound 290);
3 '-{N'-[1-N- (4-Methylbenzyl) -2,8-dioxo-1,2,7,8-tetrahydroisoquinoline-7-ylidene] hydrazino} -2'-hydroxybiphenyl-3 -Carboxylic acid (compound 291);
3 '-{N'-[1-N-benzyl-2,8-dioxo-1,2,7,8-tetrahydroisoquinoline-7-ylidene] hydrazino} -2'-hydroxybiphenyl-3-carboxylic acid (compound 292);
3 '-{N'-[1-N- (4-trifluoromethylphenyl) -2,8-dioxo-1,2,7,8-tetrahydroisoquinoline-7-ylidene] hydrazino} -2'-hydroxybiphenyl -3-carboxylic acid (compound 293);
3 '-{N'-[1-N- (3-trifluoromethylphenyl) -2,8-dioxo-1,2,7,8-tetrahydroisoquinoline-7-ylidene] hydrazino} -2'-hydroxybiphenyl -3-carboxylic acid (compound 294);
3 '-{N'-[1-N- (3,5-Dimethylphenyl) -2,8-dioxo-1,2,7,8-tetrahydroisoquinoline-7-ylidene] hydrazino} -2'-hydroxybiphenyl -3-carboxylic acid (compound 295);
3 '-{N'-[1-N-phenyl-2,8-dioxo-1,2,7,8-tetrahydroisoquinoline-7-ylidene] hydrazino} -2'-hydroxybiphenyl-3-carboxylic acid (compound 296);
3 '-{N'-[1-N- (3,4-Dimethylphenyl) -2,8-dioxo-1,2,7,8-tetrahydroisoquinoline-7-ylidene] hydrazino} -2'-hydroxybiphenyl -3-carboxylic acid (Compound 297);
3 '-{N'-[1-N- (3,4-Dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -2'-fluorobiphenyl -3-carboxylic acid (compound 298);
3- (3- {N '-[1-N- (3,4-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -2-hydroxy Phenyl) -2 (Z) -propenoic acid (compound 299);
3- (3- {N '-[1-N- (3,4-dimethylphenyl) -2-oxo-4-fluoro-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -2-hydroxyphenyl) -2 (Z) -propenoic acid (compound 300);
5- (3- {N '-[1- (3,4-dimethylphenyl) -2-oxo-4-fluoro-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -2 -Hydroxybenzylidene) thiazolidine-2,4-dione (compound 301);
2-Chloro-3- (4- {N '-[1- (3,4-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -3 -Hydroxyphenyl) -2-propenoic acid (Compound 302);
2-Ethyl-3- (4- {N '-[1- (3,4-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -3 -Hydroxyphenyl) -2-propenoic acid (compound 303);
1-N-methyl-5- (4- {N '-[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -3-hydroxybenzylidene) -1,3-diazolidine-2,4-dione (compound 304);
5- (4- {N '-[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -3-hydroxybenzylidene) -1,3-diazolidine-2,4-dione (Compound 305);
2-Fluoro-3- (4- {N '-[1- (3,4-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -3 -Hydroxyphenyl) -2-propenoic acid (Compound 306);
(±) -2-Methoxy-3- (4- {N '-[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] Hydrazino} -3-hydroxyphenyl) propanoic acid (compound 307);
4- (3- {N '-[1- (3,4-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -2-hydroxyphenyl) Butanoic acid (Compound 308);
3- (2- {N '-[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -3-hydroxyphenoxy) Propanoic acid (compound 309);
4- (4- {N '-[1- (3,4-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -3-hydroxyphenyl) Butanoic acid (compound 310),
And pharmaceutically acceptable salts, esters, amides or prodrugs of the compound.

  In certain embodiments, the present invention provides any single compound selected from any of the compounds in the list above. In certain embodiments, the present invention provides any number and any combination of compounds selected from the compounds in the list above.

  The compounds of the present invention may exist as stereoisomers (including optical isomers). The disclosure of the present invention covers both all stereoisomers and racemic mixtures of the stereoisomers, as well as individual enantiomers, which can be separated according to methods known in the art or preferentially compared to the other. Can be removed by synthetic schemes known in the art designed to yield one enantiomer.

を用いて製造することができる。 (Synthesis method)
In certain embodiments, the compounds of the invention have the following reaction scheme:

Can be used.

The production method of Reaction Scheme 1 is a multi-step synthesis sequence. This begins with palladium-catalyzed cross-coupling with phenylboronic acid (eg, structure 2) and aryl bromide (eg, structure 1) to give biaryl structure 3. Deprotection of the methyl ether is performed followed by nitration and hydrogenation to give the biphenyl amino acid (eg, structure 4). The amino group is then diazotized under standard conditions and treated with a suitable coupling partner to give the final product of structure 6.

Scheme II is a multi-step synthetic sequence. This begins with a copper catalyzed cross-coupling of an oxoindole (eg, structure 7) with an aryl or alkyl bromide to give an N-substituted oxoindole of structure 8. This is then followed by coupling the N-substituted oxoindole with a diazonium salt of a biphenyl amino acid (eg, structure 4) to give the final product of structure 9.

The process of reaction formula III is a multi-step synthesis sequence. This begins with reductive amination of aniline (eg, structure 10) with benzaldehyde and conversion of structure 11 to chloroacetanilide with chloroacetyl chloride. Palladium-catalyzed ring closure yields N-benzyloxoindole (eg, structure 12), which is then coupled with a diazonium salt of the structure 4 biphenyl amino acid to give the final product of structure 9.

The process of reaction formula IV is a multi-step synthesis sequence. This begins with the conversion of the amine of structure 13 to an N-aryl rhodanine using bis (carboxymethyl) trithiocarbonate. The rhodanine is then coupled with a diazonium salt of a biphenyl amino acid (eg, structure 4) to give the final product of structure 15.

  In Scheme V, hydroxynitrobenzaldehyde (eg, structure 16) is converted to either a cinnamate (structure 17) or a thiazolidinedione derivative (eg, structure 19). The essential nitro group is reduced and then coupled with the corresponding N-aryloxoindole of structure 8 to give the final compound of structure 20.

  One skilled in the art will recognize that similar compounds can be prepared using similar synthetic schemes. One skilled in the art will recognize that the compounds of the invention can be prepared using other synthetic schemes. In certain embodiments, the present invention provides a salt corresponding to any of the compounds provided herein.

  In certain embodiments, the present invention provides salts corresponding to selective TPO modifiers. In certain embodiments, the present invention provides salts corresponding to selective TPO receptor binding agents. In certain embodiments, the salt reacts the compound with an acid (eg, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, etc.). Get by. In certain embodiments, the salt is obtained by reacting the compound with a base to produce a salt (eg, an ammonium salt, an alkali metal salt (eg, a sodium salt or a potassium salt), an alkaline earth metal salt (eg, a calcium salt or a magnesium salt). Organic bases (eg, choline, dicyclohexylamine, N-methyl-D-glucamine, tris (hydroxymethyl) methylamine, 4- (2-hydroxyethyl) -morpholine, 1- (2-hydroxyethyl) -pyrrolidine, ethanol Amine), and amino acid (eg, arginine, lysine, etc.) In certain embodiments, the salt can convert the free acid form of the selective TPO modifier or the selective TPO binding agent to Reacting with an equivalent amount of base (eg bis-sodium, bis-ethanolamine, etc.) Get me.

  In certain embodiments, the salts corresponding to the compounds of the present invention are acetic acid, ammonium, benzenesulfonic acid, benzoic acid, hydrogen carbonate, hydrogen sulfate, hydrogen tartaric acid, boric acid, bromide, calcium edetate, kansylic acid, carbonic acid, chloride. , Cholinate, clavulanic acid, citric acid, dihydrochloric acid, diphosphoric acid, edetic acid, edisylate, estolate, esylate, fumaric acid, gluceptate, glucone Acid, glutamate, glucolylarsanilate, hexylresorcinate, hydrabanine, hydrogen bromide, hydrochloric acid, hydroxynaphthoic acid, iodo, isethionic acid, lactate, lactobionic acid, lauric acid , Magnesium, malate, maleate, mandelate, mucate, napsi Napsylate, nitrate, N-methylglucamine, oxalate, pamoate (embonate), palmitic acid, pantothenic acid, phosphate, polygalacturonic acid, potassium, salicylate, sodium, stearic acid Selected from salts of salts, subaceatate, succinate, sulfate, tannic acid, tartaric acid, theocric acid, tosylate salt, triethiodide, tromethamine, trimethylaminemonium, and valeric acid.

  In certain embodiments, one or more carbon atoms of the compounds of the invention are substituted with silicon. For example, WO 03 / 037905A1; by Tacke and Zilch, Endeavor, New Series, 10, 191-197 (1986); and by Bains and Tacke, Curr. Opin. Drug See Discov Devel. Jul: 6 (4): 526-43 (2003). In certain embodiments, compounds of the present invention that contain one or more silicon atoms are larger in the patient when compared to the desired properties (eg, the same compound in which none of the carbon atoms are replaced by silicon atoms). Stability and / or longer half-life).

(Assay)
In certain embodiments, the compounds of the invention can be used in any of a variety of assays. For example, the compounds of the present invention can be used in luciferase assays (eg, by Lamb et al., Nucleic Acids Research, 23: 3283-3289 (1995), and / or by Seidel et al., Proc. Nat. Acad. Sci. USA; 92: 3041-3045 (1995)) can be tested for potency as a selective TPO modifier.

  The compounds of the present invention can be used in in vitro proliferation and / or differentiation assays (eg, by Bartley et al., Cell, 77: 1117-1124 (1994), and / or by Cwirla et al., Science, 276: 1696. -1699 (1997)).

(Pharmaceutical composition)
In certain embodiments, at least one selective TPO modifier, or a pharmaceutically acceptable salt, ester, amide and / or prodrug thereof, in combination with one or more pharmaceutically acceptable carriers, A pharmaceutical composition is produced. Techniques for formulating and administering compounds of the present invention can be found, for example, in “Remington's Pharmaceutical Sciences,” Mack Publishing Co., Easton, PA, 18th edition, 1990.

  In certain embodiments, pharmaceutical compositions containing one or more of the compounds of the present invention can be prepared using known techniques (eg, mixing, dissolving, granulating, dragee-making, kneading, emulsifying, encapsulating. Including, but not limited to, entrapment or tableting processes.

  In certain embodiments, a pharmaceutical composition containing one or more compounds of the invention is a liquid (eg, a suspension, elixir, and / or solution). In such embodiments, liquid pharmaceutical compositions containing one or more compounds of the present invention include ingredients known in the art (eg, water, glycols, oils, alcohols, fragrances, preservatives, and colorants). But is not limited to these).

  In certain embodiments, a pharmaceutical composition containing one or more compounds of the present invention is a solid (eg, a powder, tablet, and / or capsule). In such embodiments, a solid pharmaceutical composition containing one or more compounds of the present invention comprises ingredients known in the art (eg, starches, sugars, diluents, granulating agents, lubricants, binders, and Including, but not limited to, disintegrants.

  In certain embodiments, a pharmaceutical composition containing one or more compounds of the present invention is formulated as a depot preparation. Such depot formulations typically work longer than non-depot formulations. In certain embodiments, the formulation is administered by implantation (eg, subcutaneously or intramuscularly) or by intramuscular injection. In certain embodiments, the depot formulation is made of a suitable polymeric or hydrophobic material (eg, an emulsion in an acceptable oil) or ion exchange resin, or slightly sparingly soluble. Manufactured as a derivative (for example, a slightly insoluble salt).

  In certain embodiments, a pharmaceutical composition containing one or more compounds of the present invention comprises a delivery system. Examples of delivery systems include, but are not limited to, liposomes and emulsions. The delivery system is useful for producing certain pharmaceutical compositions (eg, pharmaceutical compositions containing hydrophobic compounds). In certain embodiments, certain organic solvents (eg, dimethyl sulfoxide) are used.

  In certain embodiments, a pharmaceutical composition containing one or more compounds of the present invention is one or more tissues designed to deliver one or more compounds of the present invention to a specific tissue or cell type. -Contain specific delivery molecules. For example, in certain embodiments, the pharmaceutical composition comprises liposomes coated with a tissue-specific antibody.

In certain embodiments, a pharmaceutical composition containing one or more compounds of the present invention comprises a co-solvent system. The co-solvent system includes, for example, benzyl alcohol, a nonpolar surfactant, a water-miscible organic polymer, and an aqueous phase. In certain embodiments, the co-solvent system is used for hydrophobic compounds. Non-limiting examples of cosolvent system is the VPD cosolvent system, which is, 3w / v% benzyl alcohol, 8w / v% nonpolar surfactant Polysorbate 80 ^(TM), and 65 w / v% It is a solution of absolute ethanol containing polyethylene glycol 300. The proportions of the cosolvent systems can vary considerably without significantly changing their solubility and toxicity properties. Moreover, it is possible to change the identity of the cosolvent components; for example, it is possible to use other surfactants in place of polysorbate 80 ^(TM); can change the fraction size of polyethylene glycol; Other biocompatible polymers (eg, polyvinylpyrrolidone) can replace polyethylene glycol; and other sugars or polysaccharides can replace glucose.

  In certain embodiments, a pharmaceutical composition containing one or more compounds of the present invention comprises a sustained release system. A non-limiting example of the sustained release system is a semi-permeable matrix of solid hydrophobic polymer. In certain embodiments, sustained release systems release compounds over a period of hours, days, weeks, or months, depending on their chemical nature.

  In certain embodiments, pharmaceutical compositions containing the compounds of the invention are prepared for oral administration. In such embodiments, the pharmaceutical composition is formulated by combining one or more compounds of the invention with a pharmaceutically acceptable carrier. The carrier formulates the compounds of the invention as tablets, pills, dragees, capsules, solutions, gels, syrups, slurries, suspensions, and other agents for oral ingestion by patients. It is possible to do. In certain embodiments, a pharmaceutical composition for oral use is obtained by mixing one or more compounds of the present invention with one or more excipients. Suitable excipients include fillers (eg, sugars (including lactose, sucrose, mannitol, or sorbitol); cellulose products (eg, corn starch, wheat starch, rice starch, potato starch, gelatin, tragacanth gum, Methyl cellulose, hydroxypropyl methyl cellulose, sodium carboxymethyl cellulose, and / or polyvinyl pyrrolidone (PVP)) In certain embodiments, the mixture is optionally ground and an auxiliary is optionally added. In embodiments, the pharmaceutical composition is produced to obtain a tablet or dragee core.In certain embodiments, a disintegrant (eg, cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof (eg, sodium alginate). Add Umm)).

  In some embodiments, the dragee core is provided with a coating. In such embodiments, concentrated saccharide solutions can be used, which optionally include gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, and / or titanium dioxide, lacquer solutions, and suitable Various organic solvents or solvent mixtures. Dyestuffs or pigments can be added to the tablets or dragee coatings.

  In certain embodiments, the pharmaceutical composition for oral administration is a push-fit capsule made of gelatin. The push-fit capsules contain one or more compounds of the invention, one or more fillers (eg lactose), binders (eg starch), and / or lubricants (eg talc or stearin). Magnesium acid), optionally mixed with a stabilizer. In certain embodiments, pharmaceutical compositions for oral administration are soft seal capsules made of gelatin and a plasticizer (eg, glycerol or sorbitol). In certain soft capsules, one or more compounds of the invention are dissolved or suspended in a suitable liquid (eg, fatty oil, liquid paraffin, or liquid polyethylene glycol). In addition, stabilizers can be added.

  In certain embodiments, a pharmaceutical composition for buccal administration is prepared. The pharmaceutical composition is a tablet or lozenge formulated in the usual manner.

  In certain embodiments, a pharmaceutical composition is prepared for administration by injection (eg, intravenous, subcutaneous, intramuscular, etc.). In such embodiments, the pharmaceutical composition includes a carrier and an aqueous solution (eg, water, a physiologically compatible buffer (eg, Hanks solution, Ringer's solution, or physiological saline buffer). In certain embodiments, other ingredients (eg, ingredients that aid solubility or function as preservatives) are included.In certain embodiments, injectable suspensions are suitable liquid carriers, The pharmaceutical composition for injection is provided in a unit dosage form (for example, an ampoule or a multi-dose container) The pharmaceutical composition for injection is oily or aqueous. Suspensions, solutions, or emulsions in the vehicle, which may include formulation agents (eg, suspending, stabilizing, and / or dispersing agents). Doctor for injection Suitable solvents for use in the composition include, but are not limited to, lipophilic solvents and fatty oils (eg, sesame oil, synthetic fatty acid esters (eg, ethyl oleate or triglycerides), and liposomes. Injectable suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Agents that increase the solubility of the compound may also be included to allow for the production of concentrated solutions.

  In certain embodiments, a pharmaceutical composition for transmucosal administration is prepared. In this embodiment, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art.

  In certain embodiments, a pharmaceutical composition is prepared for administration by inhalation. The pharmaceutical composition for inhalation is manufactured in the form of an aerosol spray in a pressurized pack or nebulizer. The pharmaceutical composition includes a propellant (eg, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, or other suitable gas). In certain embodiments using a pressurized aerosol, the dosage unit can be determined using a valve that carries a metered amount. In certain embodiments, capsules and drug packages for use in inhalers or insufflators can be manufactured. The formulations comprise a powder mixture of a compound of the invention and a suitable powder base (eg lactose or starch).

  In certain embodiments, pharmaceutical compositions (eg, suppositories or retention enemas) for rectal administration are prepared. The pharmaceutical composition includes known ingredients (eg, cocoa butter and / or other glycerides).

In certain embodiments, a pharmaceutical composition for topical administration is manufactured. The pharmaceutical composition includes a bland wet base (eg, an ointment or cream). Exemplary ointment bases include petrolatum, petrolatum and volatile silicones, lanolin, and water in oil emulsions (eg, Euserin® ⁽ available from Cincinnati, Ohio)) but not limited thereto. exemplary suitable cream base (available from Beiersdorf, Inc. (Cincinnati, Ohio)) Nivea ^(TM) Cream, cold cream (USP), purpose Cream ^(TM) ( This includes, but is not limited to, Johnson & Johnson (New Brunswick, New Jersey), hydrophilic cartilage (USP), and Lubriderm ⁽ available from Morris Plains, New Jersey).

  In certain embodiments, a pharmaceutical composition containing one or more compounds of the present invention comprises the active ingredient in a therapeutically effective amount. In certain embodiments, a therapeutically effective amount is sufficient to prevent, reduce, or ameliorate symptoms of disease or prolong the survival of the subject being treated. The determination of a therapeutically effective amount is well within the ability of those skilled in the art.

  In certain embodiments, one or more compounds of the invention are formulated as a prodrug. In certain embodiments, after in vivo administration, the prodrug is converted to a biologically, pharmaceutically or therapeutically more active form of the compound. In certain embodiments, prodrugs are useful because they are easier to administer than the corresponding active form. For example, in some cases, prodrugs are more bioavailable (eg, by oral administration) than the corresponding active form. In some cases, prodrugs may have improved solubility compared to the corresponding active form. In certain embodiments, the prodrug is less water soluble than the corresponding active form. In certain instances, the prodrug has excellent passage through the cell membrane (where water solubility is detrimental to mobility). In certain embodiments, the prodrug is an ester. In certain embodiments, the ester is hydrolyzed metabolically to a carboxylic acid after administration. In certain instances, the compound containing the carboxylic acid is the corresponding active form. In certain embodiments, the prodrug comprises a short peptide (polyamino acid) linked to an acidic group. In this embodiment, the peptide is cleaved after administration to produce the corresponding active form.

  In certain embodiments, prodrugs are produced by modifying a pharmaceutically active compound such that the active compound will regenerate after in vivo administration. The prodrug may be used to alter the metabolic stability or delivery properties of the drug, mask side effects or toxicity, improve the flavor of the drug, or alter other attributes or properties of the drug. Can be designed. With knowledge of pharmacodynamic processes and in vivo drug metabolism, one of ordinary skill in the art can design prodrugs of compounds once they know a pharmaceutically active compound (eg, Nogrady (1985) Medicinal Chemistry A Biochemical Approach, Oxford University Press, New York, pages 388-392).

  In certain embodiments, pharmaceutical compositions containing one or more compounds of the invention are useful for treating a disease or disorder in a mammalian (particularly human) patient. Suitable routes of administration are oral, rectal, transmucosal, intestine, enteral, topical, suppository, inhalation, intrathecal, intraventricular, intraperitoneal, intranasal, intraocular, and parenteral (eg, intravenous, Including, but not limited to, intramuscular, intramedullary, and subcutaneous). In certain embodiments, the pharmaceutical intrathecal drug is administered to be local rather than systemic exposure. For example, the pharmaceutical composition can be injected directly into the area of the desired effect (eg, into the kidney or heart area).

  In certain embodiments, pharmaceutical compositions containing one or more compounds of the invention are administered in dosage unit form (eg, tablets, capsules, boluses, etc.). In certain embodiments, the dosage unit comprises a selective TPO modulator at a dose of about 1 μg / kg body weight to about 50 mg / kg body weight. In certain embodiments, the dosage unit comprises a selective TPO modulator at a dose of about 2 μg / kg body weight to about 25 mg / kg body weight. In certain embodiments, the dosage unit comprises a selective TPO modulator at a dose of about 10 μg / kg body weight to about 5 mg / kg body weight. In certain embodiments, the pharmaceutical composition is administered as needed once a day, twice a day, three times a day, or four or more times a day. Those skilled in the art will appreciate that the dosage, number of times and duration of administration depend on a number of factors including, but not limited to, the desired biological activity, patient illness, and tolerance to the pharmaceutical composition. You will admit it depends.

  In certain embodiments, the formulation, route of administration, and dosage of the pharmaceutical composition of the invention can be selected in terms of patient illness (eg, by Fingl et al., 1975, “The Pharmacological Basis of Therapeutics ”, Chapter 1, page 1). In certain embodiments, the pharmaceutical composition is administered as a single dose. In certain embodiments, the pharmaceutical composition is administered as a series of two or more doses administered over a day or more.

In certain embodiments, a pharmaceutical composition of the invention is administered to a patient between about 0.1% and 500% (more preferably between about 25% and 75%) of an established human dose. If a human dose is not probable, an appropriate human dose can be inferred from ED ₅₀ or ID ₅₀ values, or other suitable values derived from in vitro or in vivo studies.

  In certain embodiments, a daily dosage regimen for a patient comprises between 0.1 mg and 2000 mg of an oral dose of a compound of the invention. In certain embodiments, a daily dosage regimen is administered as a single daily dosage. In certain embodiments, the daily dosage regimen is administered as 2, 3, 4, or more than 4 doses.

  In certain embodiments, the pharmaceutical composition of the invention is administered by continuous intravenous infusion. In such embodiments, 0.1 mg to 500 mg of the composition of the invention is administered daily.

  In certain embodiments, the pharmaceutical composition of the invention is administered over a period of continuous treatment. For example, the pharmaceutical compositions of the invention can be administered over a period of days, weeks, months, or years.

  Dosages, intervals of administration, and duration of treatment can be adjusted to achieve the desired effect. In certain embodiments, doses and intervals of administration are adjusted to maintain the desired concentration of the compound in the patient. For example, in certain embodiments, dosages and intervals of administration are adjusted to obtain a blood concentration of a compound of the invention in an amount sufficient to achieve the desired effect. In the embodiment, the blood concentration is kept above a minimum effective concentration (MEC). In certain embodiments, the pharmaceutical composition of the invention is designed to maintain a concentration above the MEC at 10-90% of the time, 30-90% of the time, or 50-90% of the time. Dosage regimen to be administered.

  In certain embodiments in which the pharmaceutical composition is administered topically, the dosage regime is administered to achieve the desired local concentration of the compound of the invention.

  In certain embodiments, the pharmaceutical composition can be provided in a package or dispenser device, which can include one or more unit dosage forms containing the active ingredients. The package may include, for example, a metal or plastic foil (eg, a blister package). The packaging or dispenser device can be accompanied by instructions for administration. The packaging or dispenser can also be accompanied by precautions relating to the container in a form prescribed by an administrative agency that controls the manufacture, use, or sale of the pharmaceutical product. Here, the notes reflect the agency's approval for the form of the drug for human or veterinary administration. The notice may be, for example, a label approved by the Federal Food and Drug Administration for prescription drugs, or a package insert of an approved product. A composition containing a compound of the invention formulated in a compatible pharmaceutical carrier may also be manufactured, placed in a suitable container, and labeled for the treatment of a disease for which a need has been indicated. Can do.

  In certain embodiments, the pharmaceutical composition is in powder form for construction with a suitable vehicle (eg, sterile, pyrogen-free water) prior to use.

(Combination therapy)
In certain embodiments, one or more pharmaceutical compositions of the present invention are co-administered with one or more other pharmaceutical agents. In certain embodiments, the one or more other pharmaceutical agents are designed to treat the same disease or condition as the one or more pharmaceutical compositions of the invention. In certain embodiments, the one or more pharmaceutical agents are designed to treat different diseases or conditions as one or more pharmaceutical compositions of the present invention. In certain embodiments, the one or more other pharmaceutical agents are designed to treat unwanted effects of one or more pharmaceutical compositions of the present invention. In certain embodiments, one or more pharmaceutical compositions of the present invention are co-administered with another pharmaceutical agent to treat the undesirable effects of the other pharmaceutical agent. In certain embodiments, one or more pharmaceutical compositions of the present invention and one or more other pharmaceutical agents are administered simultaneously. In certain embodiments, one or more pharmaceutical compositions of the present invention and one or more other pharmaceutical agents are administered at different times. In certain embodiments, one or more pharmaceutical compositions of the present invention and one or more other pharmaceutical agents are manufactured together in a single formulation. In certain embodiments, one or more pharmaceutical compositions of the present invention and one or more other pharmaceutical agents are prepared separately.

  Examples of pharmaceutical agents that can be co-administered with the pharmaceutical composition of the present invention include, but are not limited to: Anti-cancer treatments (eg, including but not limited to chemotherapy and radiotherapy); corticosteroids (eg, including but not limited to prednisone); immunoglobulins (eg, intravenous immunoglobulin (IVIg)) Analgesics (eg, acetaminophen); anti-inflammatory agents (eg, non-steroidal anti-inflammatory agents (eg, ibuprofen, COX-1 inhibitors, and COX-2 inhibitors)) Salicylic acid; antibiotics; antiviral agents; antifungal agents; antidiabetic agents (eg, biguanides, glucosidase inhibitors, insulin, sulfonylureas, and thiazolidenediones); adrenergic modulators; Diuretics; hormonal agents (eg protein Steroids, androgens, estrogens, calcitonin, progestins, somatostan, and thyroid hormones); immunomodulators; muscle relaxants; antihistamines; osteoporosis agents (eg, biphosphonates, calcitonin, and estrogens); prostaglandins, Anti-neoplastic agents; psychotherapeutic agents; sedatives; poison oak or poison sumac products; antibodies; and vaccines.

(Indication)
In certain embodiments, the invention provides a method of treating a patient comprising administering one or more compounds of the invention. In certain embodiments, the patient suffers from thrombocytopenia. In certain embodiments, thrombocytopenia results from chemotherapy and / or radiation therapy. In certain embodiments, the thrombocytopenia results in bone marrow dysfunction due to bone marrow transplantation and / or aplastic anemia. In certain embodiments, thrombocytopenia is idiopathic. In certain embodiments, one or more compounds of the invention are administered to a patient in combination with collecting peripheral blood progenitor cells and / or in combination with platelet apheresis. The administration can take place before, during and / or after the collection.

  In certain embodiments, one or more of the compounds of the invention suffers from a disease affecting the nervous system (eg, including but not limited to diseases affecting the nervous system and damage to the nervous system). To patients. Such diseases include, but are not limited to, amyotrophic lateral sclerosis, multiple sclerosis, and multiple dystrophy. Nervous system damage includes, but is not limited to, spinal cord injury or peripheral nerve damage (including but not limited to damage caused by trauma or stroke, for example). In certain embodiments, one or more compounds of the invention are used to promote glial cell proliferation and / or development. The glial cells can repair nerve cells. In certain embodiments, the compounds of the invention are used to treat psychological disorders (eg, including but not limited to cognitive impairment). In certain embodiments, one or more compounds of the present invention are administered to increase athletic performance.

  The following examples (including experiments and results achieved) are provided for illustrative purposes only and should not be construed as limiting the invention.

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.07 (s, 1H), 13.03 (s, 1H), 9.26 (s, 1H), 8.12 (t, J=1.6 Hz, 1H), 7.94 (ddd, J=7.7, 1.6, 1.3 Hz, 1H), 7.79 (ddd, J=7.7, 1.6, 1.3 Hz, 1H), 7.73 (dd, J=7.9, 1.6 Hz, 1H), 7.72 (m, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.35 (d, J=8.1 Hz, 1H), 7.30 (d, J=2.1 Hz, 1H), 7.28 (td, J=7.7, 1.3 Hz, 1H), 7.23 (dd, J=8.1, 2.1 Hz, 1H), 7.18 (td, J=7.7, 0.9 Hz, 1H), 7.11 (t, J=7.9 Hz, 1H), 7.00 (dd, J=7.9, 1.6 Hz, 1H), 6.85 (m, 1H), 2.31 (s, 3H), 2.30 (s, 3H)。 Example 1: 3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid (Compound 101)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.07 (s, 1H), 13.03 (s, 1H), 9.26 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.3 Hz, 1H), 7.79 (ddd, J = 7.7, 1.6, 1.3 Hz, 1H), 7.73 (dd, J = 7.9, 1.6 Hz, 1H), 7.72 (m, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.35 (d, J = 8.1 Hz, 1H), 7.30 (d, J = 2.1 Hz, 1H), 7.28 (td, J = 7.7, 1.3 Hz, 1H), 7.23 (dd, J = 8.1, 2.1 Hz, 1H), 7.18 (td, J = 7.7, 0.9 Hz, 1H), 7.11 (t, J = 7.9 Hz, 1H), 7.00 (dd, J = 7.9, 1.6 Hz, 1H), 6.85 (m, 1H), 2.31 (s, 3H), 2.30 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.07 (s, 1H), 13.03 (s, 1H), 9.27 (s, 1H), 8.11 (t, J =1.6 Hz, 1H), 7.94 (dt, J =7.7, 1.6 Hz, 1H), 7.79 (dt, J =7.7, 1.6 Hz, 1H), 7.73 (d, J =7.9 Hz, 1H), 7.73 (d, J =7.9 Hz, 1H), 7.60 (t, J =7.7 Hz, 1H), 7.44 (d, J =8.5 Hz, 2H), 7.41 (d, J =8.5 Hz, 2H), 7.29 (td, J =7.7, 1.3 Hz, 1H), 7.19 (td, J =7.7, 1.0 Hz, 1H), 7.11 (t, J =7.9 Hz, 1H), 7.00 (dd, J =7.7, 1.3 Hz, 1H), 6.87 (dd, J =7.7, 1.0 Hz, 1H), 2.66 (t, J =7.3 Hz, 2H), 1.66 (６重線(sext), J =7.3 Hz, 2H), 0.95 (t, J =7.3 Hz, 3H)。 Example 2: 2′-Hydroxy-3 ′-{N ′-[2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3 -Carboxylic acid (Compound 102)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.07 (s, 1H), 13.03 (s, 1H), 9.27 (s, 1H), 8.11 (t, J = 1.6 Hz, 1H), 7.94 (dt, J = 7.7, 1.6 Hz, 1H), 7.79 (dt, J = 7.7, 1.6 Hz, 1H), 7.73 (d, J = 7.9 Hz, 1H), 7.73 (d, J = 7.9 Hz, 1H), 7.60 ( t, J = 7.7 Hz, 1H), 7.44 (d, J = 8.5 Hz, 2H), 7.41 (d, J = 8.5 Hz, 2H), 7.29 (td, J = 7.7, 1.3 Hz, 1H), 7.19 ( td, J = 7.7, 1.0 Hz, 1H), 7.11 (t, J = 7.9 Hz, 1H), 7.00 (dd, J = 7.7, 1.3 Hz, 1H), 6.87 (dd, J = 7.7, 1.0 Hz, 1H) ), 2.66 (t, J = 7.3 Hz, 2H), 1.66 (sext), J = 7.3 Hz, 2H), 0.95 (t, J = 7.3 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.06 (s, 1H), 13.03 (s, 1H), 9.27 (s, 1H), 8.11 (t, J =1.5 Hz, 1H), 7.94 (dt, J =7.8, 1.5 Hz, 1H), 7.79 (dt, J =7.8, 1.5 Hz, 1H), 7.73 (dd, J =7.8 Hz, 1H), 7.73 (dd, J =7.8 Hz, 1H), 7.60 (t, J =7.8 Hz, 1H), 7.45 (d, J =8.6 Hz, 2H), 7.43 (d, J =8.6 Hz, 2H), 7.29 (td, J =7.9, 1.0 Hz, 1H), 7.19 (td, J =7.9, 1.0 Hz, 1H), 7.11 (t, J =7.8 Hz, 1H), 7.00 (dd, J =7.9, 1.0 Hz, 1H), 6.87 (dd, J =7.9, 1.0 Hz, 1H), 2.71 (q, J =7.6 Hz, 2H), 1.25 (t, J =7.6 Hz, 3H)。 Example 3 2′-Hydroxy-3 ′-{N ′-[2-oxo-1- (4-ethyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3 -Carboxylic acid (Compound 103)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.06 (s, 1H), 13.03 (s, 1H), 9.27 (s, 1H), 8.11 (t, J = 1.5 Hz, 1H), 7.94 (dt, J = 7.8, 1.5 Hz, 1H), 7.79 (dt, J = 7.8, 1.5 Hz, 1H), 7.73 (dd, J = 7.8 Hz, 1H), 7.73 (dd, J = 7.8 Hz, 1H), 7.60 ( t, J = 7.8 Hz, 1H), 7.45 (d, J = 8.6 Hz, 2H), 7.43 (d, J = 8.6 Hz, 2H), 7.29 (td, J = 7.9, 1.0 Hz, 1H), 7.19 ( td, J = 7.9, 1.0 Hz, 1H), 7.11 (t, J = 7.8 Hz, 1H), 7.00 (dd, J = 7.9, 1.0 Hz, 1H), 6.87 (dd, J = 7.9, 1.0 Hz, 1H) ), 2.71 (q, J = 7.6 Hz, 2H), 1.25 (t, J = 7.6 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.03 (s, 1H), 9.30 (s, 1H), 8.11 (t, J =1.8 Hz, 1H), 7.94 (ddd, J =7.8, 1.8, 1.2 Hz, 1H), 7.79 (ddd, J=7.8, 1.8, 1.2 Hz, 1H), 7.75 (dd, J =7.7, 1.0 Hz, 1H), 7.74 (dd, J =7.8, 1.6 Hz, 1H), 7.72 (d, J =8.9 Hz, 2H), 7.60 (t, J =7.8 Hz, 1H), 7.31 (td, J =7.7, 1.0 Hz, 1H), 7.22 (td, J =7.7, 1.0 Hz, 1H), 7.12 (t, J =7.8 Hz, 1H), 7.01 (dd, J =7.8, 1.6 Hz, 1H), 6.94 (dd, J =7.7, 1.0 Hz, 1H)。 Example 4: 2'-hydroxy-3 '-{N'-[2-oxo-1- (4-trifluoromethoxy-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl -3-carboxylic acid (compound 104)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.03 (s, 1H), 9.30 (s, 1H), 8.11 (t, J = 1.8 Hz, 1H), 7.94 (ddd, J = 7.8, 1.8, 1.2 Hz, 1H), 7.79 (ddd, J = 7.8, 1.8, 1.2 Hz, 1H), 7.75 (dd, J = 7.7, 1.0 Hz, 1H), 7.74 (dd, J = 7.8, 1.6 Hz, 1H), 7.72 (d, J = 8.9 Hz, 2H), 7.60 (t, J = 7.8 Hz, 1H), 7.31 (td, J = 7.7, 1.0 Hz, 1H), 7.22 (td, J = 7.7, 1.0 Hz, 1H) , 7.12 (t, J = 7.8 Hz, 1H), 7.01 (dd, J = 7.8, 1.6 Hz, 1H), 6.94 (dd, J = 7.7, 1.0 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.03 (s, 1H), 9.28 (s, 1H), 8.12 (t, J =1.6 Hz, 1H), 7.94 (ddd, J =7.7, 1.6, 1.2 Hz, 1H), 7.79 (ddd, J =7.7, 1.6, 1.2 Hz, 1H), 7.74-7.71 (m, 2H), 7.60 (t, J =7.7 Hz, 1H), 7.50 (dd, J =12.3, 2.2 Hz, 1H), 7.38 (t, J =8.8 Hz, 1H), 7.35 (dd, J =8.8, 2.2 Hz, 1H), 7.29 (td, J =7.7, 1.0 Hz, 1H), 7.19 (td, J =7.7, 1.0 Hz, 1H), 7.11 (t, J =7.7 Hz, 1H), 7.00 (dd, J =7.7, 1.6 Hz, 1H), 6.87 (dd, J =7.7, 1.0 Hz, 1H), 3.93 (s, 3H)。 Example 5: 3 ′-{N ′-[1- (3-Fluoro-4-methoxy-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy -Biphenyl-3-carboxylic acid (Compound 105)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.03 (s, 1H), 9.28 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.74-7.71 (m, 2H), 7.60 (t, J = 7.7 Hz, 1H), 7.50 (dd, J = 12.3, 2.2 Hz, 1H), 7.38 (t, J = 8.8 Hz, 1H), 7.35 (dd, J = 8.8, 2.2 Hz, 1H), 7.29 (td, J = 7.7, 1.0 Hz, 1H), 7.19 (td, J = 7.7, 1.0 Hz, 1H), 7.11 (t, J = 7.7 Hz, 1H), 7.00 (dd, J = 7.7, 1.6 Hz, 1H), 6.87 (dd, J = 7.7, 1.0 Hz, 1H), 3.93 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.07 (s, 1H), 12.96 (s, 1H), 9.30 (s, 1H), 8.02 (d, J =8.4 Hz, 2H), 7.74 (dd, J =7.8, 1.6 Hz, 1H), 7.72 (dd, J =7.7, 1.0 Hz, 1H), 7.68 (d, J =8.4 Hz, 2H), 7.35 (d, J =8.0 Hz, 1H), 7.30 (m, 1H), 7.27 (td, J =7.7, 1.0 Hz, 1H), 7.23 (dd, J =8.0, 2.1 Hz, 1H), 7.18 (td, J =7.7, 1.0 Hz, 1H), 7.12 (t, J =7.8 Hz, 1H), 7.01 (dd, J =7.8, 1.6 Hz, 1H), 6.85 (dd, J =7.7, 1.0 Hz, 1H), 2.31 (s, 3H), 2.30 (s, 3H)。 Example 6: 3 ′-{N ′-[1- (3,4-Dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy-biphenyl -4-carboxylic acid (compound 106)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.07 (s, 1H), 12.96 (s, 1H), 9.30 (s, 1H), 8.02 (d, J = 8.4 Hz, 2H), 7.74 (dd, J = 7.8, 1.6 Hz, 1H), 7.72 (dd, J = 7.7, 1.0 Hz, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.0 Hz, 1H), 7.30 ( m, 1H), 7.27 (td, J = 7.7, 1.0 Hz, 1H), 7.23 (dd, J = 8.0, 2.1 Hz, 1H), 7.18 (td, J = 7.7, 1.0 Hz, 1H), 7.12 (t , J = 7.8 Hz, 1H), 7.01 (dd, J = 7.8, 1.6 Hz, 1H), 6.85 (dd, J = 7.7, 1.0 Hz, 1H), 2.31 (s, 3H), 2.30 (s, 3H) .

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.06 (s, 1H), 12.96 (s, 1H), 9.31 (s, 1H), 8.02 (d, J=8.3 Hz, 2H), 7.75-7.72 (m, 2H), 7.68 (d, J=8.3 Hz, 2H), 7.44 (d, J =8.6 Hz, 2H), 7.41 (d, J =8.6 Hz, 2H), 7.29 (td, J =7.7, 1.0 Hz, 1H), 7.19 (td, J =7.7, 1.0 Hz, 1H), 7.12 (t, J =7.8 Hz, 1H), 7.01 (dd, J =7.8, 1.6 Hz, 1H), 6.87 (dd, J=7.7, 1.0 Hz, 1H), 2.66 (t, J=7.4 Hz, 2H), 1.66 (sext, J=7.4 Hz, 2H), 0.95 (t, J=7.4 Hz, 3H)。 Example 7: 2′-Hydroxy-3 ′-{N ′-[2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-4 -Carboxylic acid (Compound 107)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.06 (s, 1H), 12.96 (s, 1H), 9.31 (s, 1H), 8.02 (d, J = 8.3 Hz, 2H), 7.75-7.72 ( m, 2H), 7.68 (d, J = 8.3 Hz, 2H), 7.44 (d, J = 8.6 Hz, 2H), 7.41 (d, J = 8.6 Hz, 2H), 7.29 (td, J = 7.7, 1.0 Hz, 1H), 7.19 (td, J = 7.7, 1.0 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 7.01 (dd, J = 7.8, 1.6 Hz, 1H), 6.87 (dd, J = 7.7, 1.0 Hz, 1H), 2.66 (t, J = 7.4 Hz, 2H), 1.66 (sext, J = 7.4 Hz, 2H), 0.95 (t, J = 7.4 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.21 (s, 1H), 8.47 (s, 1H), 8.11 (d, J =8.5 Hz, 2H), 7.79 (dd, J =7.8, 1.6 Hz, 1H), 7.76 (m, 1H), 7.68 (d, J =8.5 Hz, 2H), 7.47 (d, J =8.5 Hz, 2H), 7.45 (d, J =8.5 Hz, 2H), 7.29 (td, J =7.7, 1.1 Hz, 1H), 7.19 (td, J =7.7, 1.1 Hz, 1H), 7.12 (t, J =7.8 Hz, 1H), 7.02 (dd, J =7.8, 1.6 Hz, 1H), 6.92 (dd, J =7.7, 1.1 Hz, 1H), 2.75 (q, J =7.6 Hz, 2H), 1.29 (t, J =7.6 Hz, 3H)。 Example 8: 2′-Hydroxy-3 ′-{N ′-[2-oxo-1- (4-ethyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-4 -Carboxylic acid (compound 108)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.21 (s, 1H), 8.47 (s, 1H), 8.11 (d, J = 8.5 Hz, 2H), 7.79 (dd, J = 7.8, 1.6 Hz, 1H), 7.76 (m, 1H), 7.68 (d, J = 8.5 Hz, 2H), 7.47 (d, J = 8.5 Hz, 2H), 7.45 (d, J = 8.5 Hz, 2H), 7.29 (td, J = 7.7, 1.1 Hz, 1H), 7.19 (td, J = 7.7, 1.1 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 7.02 (dd, J = 7.8, 1.6 Hz, 1H), 6.92 (dd, J = 7.7, 1.1 Hz, 1H), 2.75 (q, J = 7.6 Hz, 2H), 1.29 (t, J = 7.6 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, アセトン-d₆) δ 13.22 (s, 1H), 8.20 (s, 1H), 8.02 (d, J =7.8 Hz, 1H), 7.80-7.74 (m, 3H), 7.64 (d, J =8.0 Hz, 2H), 7.58 (m, 1H), 7.48 (d, J =8.0 Hz, 2H), 7.29 (t, J =7.7 Hz, 1H), 7.19 (t, J =7.7 Hz, 1H), 7.11 (t, J =7.8 Hz, 1H), 7.00 (m, 1H), 6.92 (d, J =7.7 Hz, 1H), 1.38 (s, 9H)。 Example 9: 3 ′-{N ′-[1- (4-tert-butyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy-biphenyl -3-carboxylic acid (compound 109)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, acetone-d ₆ ) δ 13.22 (s, 1H), 8.20 (s, 1H), 8.02 (d, J = 7.8 Hz, 1H), 7.80-7.74 (m, 3H), 7.64 ( d, J = 8.0 Hz, 2H), 7.58 (m, 1H), 7.48 (d, J = 8.0 Hz, 2H), 7.29 (t, J = 7.7 Hz, 1H), 7.19 (t, J = 7.7 Hz, 1H), 7.11 (t, J = 7.8 Hz, 1H), 7.00 (m, 1H), 6.92 (d, J = 7.7 Hz, 1H), 1.38 (s, 9H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.04 (s, 1H), 9.32 (s, 1H), 8.12 (t, J =1.5 Hz, 1H), 7.98 (d, J =8.5 Hz, 2H), 7.94 (dt, J =7.7, 1.5 Hz, 1H), 7.83 (d, J =8.5 Hz, 2H), 7.79 (dt, J =7.7, 1.5 Hz, 1H), 7.77 (d, J =7.8 Hz, 1H), 7.74 (dd, J =7.6, 1.2 Hz, 1H), 7.59 (t, J =7.7 Hz, 1H), 7.32 (td, J =7.6, 1.2 Hz, 1H), 7.24 (td, J =7.6, 1.2 Hz, 1H), 7.12 (t, J =7.8 Hz, 1H), 7.04 (d, J =7.8 Hz, 1H), 7.02 (dd, J =7.6, 1.2 Hz, 1H)。 Example 10: 2′-Hydroxy-3 ′-{N ′-[2-oxo-1- (4-trifluoromethyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl -3-carboxylic acid (compound 110)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.04 (s, 1H), 9.32 (s, 1H), 8.12 (t, J = 1.5 Hz, 1H), 7.98 (d, J = 8.5 Hz, 2H) , 7.94 (dt, J = 7.7, 1.5 Hz, 1H), 7.83 (d, J = 8.5 Hz, 2H), 7.79 (dt, J = 7.7, 1.5 Hz, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.74 (dd, J = 7.6, 1.2 Hz, 1H), 7.59 (t, J = 7.7 Hz, 1H), 7.32 (td, J = 7.6, 1.2 Hz, 1H), 7.24 (td, J = 7.6 , 1.2 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 7.04 (d, J = 7.8 Hz, 1H), 7.02 (dd, J = 7.6, 1.2 Hz, 1H).

この化合物は、反応式ＩＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.10 (s, 1H), 13.03 (s, 1H), 9.36 (s, 1H), 8.13 (t, J =1.7 Hz, 1H), 7.95 (ddd, J =7.7, 1.7, 1.3 Hz, 1H), 7.80 (ddd, J=7.7, 1.7, 1.3 Hz, 1H), 7.76 (dd, J=7.7, 1.6 Hz, 1H), 7.68 (d, J=2.1 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.37-7.32 (m, 4H), 7.30 (dd, J=8.5, 2.1 Hz, 1H), 7.27 (m, 1H), 7.11 (t, J=7.7 Hz, 1H), 7.09 (d, J=8.5 Hz, 1H), 7.03 (dd, J=7.7, 1.6 Hz, 1H), 5.05 (s, 2H)。 Example 11: 3 ′-[N ′-(1-Benzyl-5-chloro-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2′-hydroxy-biphenyl-3-carboxylic acid Acid (compound 111)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.10 (s, 1H), 13.03 (s, 1H), 9.36 (s, 1H), 8.13 (t, J = 1.7 Hz, 1H), 7.95 (ddd, J = 7.7, 1.7, 1.3 Hz, 1H), 7.80 (ddd, J = 7.7, 1.7, 1.3 Hz, 1H), 7.76 (dd, J = 7.7, 1.6 Hz, 1H), 7.68 (d, J = 2.1 Hz , 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.37-7.32 (m, 4H), 7.30 (dd, J = 8.5, 2.1 Hz, 1H), 7.27 (m, 1H), 7.11 (t, J = 7.7 Hz, 1H), 7.09 (d, J = 8.5 Hz, 1H), 7.03 (dd, J = 7.7, 1.6 Hz, 1H), 5.05 (s, 2H).

この化合物は、反応式ＩＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.04 (s, 1H), 13.03 (s, 1H), 9.25 (s, 1H), 8.13 (t, J=1.5 Hz, 1H), 7.94 (dt, J=7.8, 1.5 Hz, 1H), 7.80 (m, 1H), 7.69 (dd, J=7.8, 1.6 Hz, 1H), 7.60 (t, J=7.8 Hz, 1H), 7.48 (d, J=1.8 Hz, 1H), 7.37-7.31 (m, 4H), 7.27 (m, 1H), 7.10 (t, J=7.8 Hz, 1H), 7.07 (dd, J=8.1, 1.8 Hz, 1H), 6.99 (dd, J=7.8, 1.6 Hz, 1H), 6.95 (d, J=8.1 Hz, 1H), 5.01 (s, 2H), 2.33 (s, 3H)。 Example 12: 3 ′-[N ′-(1-Benzyl-5-methyl-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2′-hydroxy-biphenyl-3-carboxylic acid Acid (Compound 112)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.04 (s, 1H), 13.03 (s, 1H), 9.25 (s, 1H), 8.13 (t, J = 1.5 Hz, 1H), 7.94 (dt, J = 7.8, 1.5 Hz, 1H), 7.80 (m, 1H), 7.69 (dd, J = 7.8, 1.6 Hz, 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.48 (d, J = 1.8 Hz, 1H), 7.37-7.31 (m, 4H), 7.27 (m, 1H), 7.10 (t, J = 7.8 Hz, 1H), 7.07 (dd, J = 8.1, 1.8 Hz, 1H), 6.99 (dd , J = 7.8, 1.6 Hz, 1H), 6.95 (d, J = 8.1 Hz, 1H), 5.01 (s, 2H), 2.33 (s, 3H).

この化合物は、反応式ＩＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.07 (s, 1H), 13.04 (s, 1H), 9.28 (s, 1H), 8.13 (t, J=1.5 Hz, 1H), 7.94 (dm, J=7.7 Hz, 1H), 7.80 (dm, J=7.7 Hz, 1H), 7.70 (dd, J=7.8, 1.3 Hz, 1H), 7.65 (d, J=7.8 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.39-7.32 (m, 4H), 7.29-7.24 (m, 2H), 7.14-7.09 (m, 2H), 7.07 (d, J=7.8 Hz, 1H), 7.00 (dd, J=7.8, 1.3 Hz, 1H), 5.05 (s, 2H)。 Example 13: 3 ′-[N ′-(1-Benzyl-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2′-hydroxy-biphenyl-3-carboxylic acid (compound 113) )

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.07 (s, 1H), 13.04 (s, 1H), 9.28 (s, 1H), 8.13 (t, J = 1.5 Hz, 1H), 7.94 (dm, J = 7.7 Hz, 1H), 7.80 (dm, J = 7.7 Hz, 1H), 7.70 (dd, J = 7.8, 1.3 Hz, 1H), 7.65 (d, J = 7.8 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.39-7.32 (m, 4H), 7.29-7.24 (m, 2H), 7.14-7.09 (m, 2H), 7.07 (d, J = 7.8 Hz, 1H), 7.00 (dd , J = 7.8, 1.3 Hz, 1H), 5.05 (s, 2H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.03 (s, 1H), 12.96 (s, 1H), 9.36 (s, 1H), 8.02 (d, J=8.3 Hz, 2H), 7.98 (d, J=8.3 Hz, 2H), 7.83 (d, J=8.3 Hz, 2H), 7.77 (dd, J=7.7, 1.2 Hz, 1H), 7.75 (dd, J=7.8, 1.6 Hz, 1H), 7.68 (d, J=8.3 Hz, 2H), 7.32 (td, J=7.7, 1.2 Hz, 1H), 7.24 (td, J=7.7, 0.7 Hz, 1H), 7.13 (t, J=7.8 Hz, 1H), 7.03 (dd, J=7.8, 1.6 Hz, 1H) 7.04 (dd, J=7.7, 0.7 Hz, 1H)。 Example 14: 2′-Hydroxy-3 ′-{N ′-[2-oxo-1- (4-trifluoromethyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl -4-carboxylic acid (compound 114)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.03 (s, 1H), 12.96 (s, 1H), 9.36 (s, 1H), 8.02 (d, J = 8.3 Hz, 2H), 7.98 (d, J = 8.3 Hz, 2H), 7.83 (d, J = 8.3 Hz, 2H), 7.77 (dd, J = 7.7, 1.2 Hz, 1H), 7.75 (dd, J = 7.8, 1.6 Hz, 1H), 7.68 ( d, J = 8.3 Hz, 2H), 7.32 (td, J = 7.7, 1.2 Hz, 1H), 7.24 (td, J = 7.7, 0.7 Hz, 1H), 7.13 (t, J = 7.8 Hz, 1H), 7.03 (dd, J = 7.8, 1.6 Hz, 1H) 7.04 (dd, J = 7.7, 0.7 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.04 (s, 1H), 13.01 (s, 1H), 9.32 (s, 1H), 8.12 (t, J=1.6 Hz, 1H), 7.95 (dt, J=7.7, 1.4 Hz, 1H), 7.93 (d, J=2.4 Hz, 1H), 7.88 (d, J=8.5 Hz, 1H), 7.79 (m, 1H), 7.75 (ddd, J=7.6, 1.0, 0.5 Hz, 1H), 7.73 (dd, J=7.7, 1.6 Hz, 1H), 7.61 (dd, J=8.5, 2.4 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.31 (td, J=7.6, 1.0 Hz, 1H), 7.22 (td, J=7.6, 0.8 Hz, 1H), 7.12 (t, J=7.7 Hz, 1H), 6.98 (ddd, J=7.6, 0.8, 0.5 Hz, 1H), 7.01 (dd, J=7.7, 1.6 Hz, 1H)。 Example 15: 3 ′-{N ′-[1- (3,4-dichloro-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy-biphenyl -3-carboxylic acid (compound 115)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.04 (s, 1H), 13.01 (s, 1H), 9.32 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.95 (dt, J = 7.7, 1.4 Hz, 1H), 7.93 (d, J = 2.4 Hz, 1H), 7.88 (d, J = 8.5 Hz, 1H), 7.79 (m, 1H), 7.75 (ddd, J = 7.6, 1.0 , 0.5 Hz, 1H), 7.73 (dd, J = 7.7, 1.6 Hz, 1H), 7.61 (dd, J = 8.5, 2.4 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.31 (td , J = 7.6, 1.0 Hz, 1H), 7.22 (td, J = 7.6, 0.8 Hz, 1H), 7.12 (t, J = 7.7 Hz, 1H), 6.98 (ddd, J = 7.6, 0.8, 0.5 Hz, 1H), 7.01 (dd, J = 7.7, 1.6 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.04 (s, 1H), 13.02 (s, 1H), 9.30 (s, 1H), 8.12 (t, J=1.6 Hz, 1H), 7.94 (ddd, J=7.8, 1.6, 1.2 Hz, 1H), 7.88 (d, J=2.0 Hz, 1H), 7.79 (ddd, J=7.8, 1.6, 1.2 Hz, 1H), 7.77 (dd, J=8.3, 2.0 Hz, 1H), 7.76-7.72 (m, 2H), 7.68 (d, J=8.3 Hz, 1H), 7.60 (t, J=7.8 Hz, 1H), 7.30 (td, J=7.7, 1.2 Hz, 1H), 7.21 (td, J=7.7, 0.9 Hz, 1H), 7.12 (t, J=7.7 Hz, 1H), 7.01 (dd, J=7.7, 1.6 Hz, 1H), 6.92 (dm, J=7.7 Hz, 1H), 2.54 (q, J=1.4 Hz, 3H)。 Example 16: 2'-hydroxy-3 '-{N'-[1- (4-methyl-3-trifluoromethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene]- Hydrazino} -biphenyl-3-carboxylic acid (compound 116)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.04 (s, 1H), 13.02 (s, 1H), 9.30 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.8, 1.6, 1.2 Hz, 1H), 7.88 (d, J = 2.0 Hz, 1H), 7.79 (ddd, J = 7.8, 1.6, 1.2 Hz, 1H), 7.77 (dd, J = 8.3, 2.0 Hz , 1H), 7.76-7.72 (m, 2H), 7.68 (d, J = 8.3 Hz, 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.30 (td, J = 7.7, 1.2 Hz, 1H) , 7.21 (td, J = 7.7, 0.9 Hz, 1H), 7.12 (t, J = 7.7 Hz, 1H), 7.01 (dd, J = 7.7, 1.6 Hz, 1H), 6.92 (dm, J = 7.7 Hz, 1H), 2.54 (q, J = 1.4 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.04 (s, 1H), 13.01 (s, 1H), 9.35 (s, 1H), 8.12 (t, J=1.7 Hz, 1H), 8.03 (t, J=8.4 Hz, 1H), 7.94 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.86 (dd, J=11.8, 1.5 Hz, 1H), 7.80 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.77 (dd, J=7.7, 1.0 Hz, 1H), 7.74 (dd, J=7.7, 1.6 Hz, 1H), 7.68 (dd, J=8.4, 1.5 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.34 (td, J=7.7, 1.0 Hz, 1H), 7.25 (td, J=7.7, 1.0 Hz, 1H), 7.14 (dd, J=7.7, 1.0 Hz, 1H), 7.12 (t, J=7.7 Hz, 1H), 7.02 (dd, J=7.7, 1.6 Hz, 1H)。 Example 17: 3 ′-{N ′-[1- (3-Fluoro-4-trifluoromethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ′ -Hydroxy-biphenyl-3-carboxylic acid (Compound 117)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.04 (s, 1H), 13.01 (s, 1H), 9.35 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 8.03 (t, J = 8.4 Hz, 1H), 7.94 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.86 (dd, J = 11.8, 1.5 Hz, 1H), 7.80 (ddd, J = 7.7, 1.7, 1.2 Hz , 1H), 7.77 (dd, J = 7.7, 1.0 Hz, 1H), 7.74 (dd, J = 7.7, 1.6 Hz, 1H), 7.68 (dd, J = 8.4, 1.5 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.34 (td, J = 7.7, 1.0 Hz, 1H), 7.25 (td, J = 7.7, 1.0 Hz, 1H), 7.14 (dd, J = 7.7, 1.0 Hz, 1H), 7.12 (t, J = 7.7 Hz, 1H), 7.02 (dd, J = 7.7, 1.6 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.04 (s, 1H), 12.99 (s, 1H), 9.34 (s, 1H), 8.38-8.37 (m, 2H), 8.27 (m, 1H), 8.12 (t, J=1.6 Hz, 1H), 7.94 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.79 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.78 (ddd, J=7.7, 1.3, 0.6 Hz, 1H), 7.75 (dd, J=7.8, 1.7 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.34 (td, J=7.7, 1.3 Hz, 1H), 7.25 (td, J=7.7, 1.0 Hz, 1H), 7.13 (t, J=7.8 Hz, 1H), 7.02 (dd, J=7.8, 1.7 Hz, 1H), 7.02 (ddd, J=7.7, 1.0, 0.6 Hz, 1H)。 Example 18: 3 ′-{N ′-[1- (3,5-bis-trifluoromethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ′ -Hydroxy-biphenyl-3-carboxylic acid (Compound 118)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.04 (s, 1H), 12.99 (s, 1H), 9.34 (s, 1H), 8.38-8.37 (m, 2H), 8.27 (m, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.78 (ddd, J = 7.7, 1.3, 0.6 Hz, 1H), 7.75 (dd, J = 7.8, 1.7 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.34 (td, J = 7.7, 1.3 Hz, 1H), 7.25 (td, J = 7.7, 1.0 Hz, 1H), 7.13 (t, J = 7.8 Hz, 1H), 7.02 (dd, J = 7.8, 1.7 Hz, 1H), 7.02 (ddd, J = 7.7, 1.0, 0.6 Hz, 1H).

この化合物は、反応式ＩＶに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 12.83 (s, 1H), 10.76 (s, 1H), 9.35 (s, 1H), 8.15 (t, J=1.5 Hz, 1H), 7.91 (m, 1H), 7.79 (dt, J=7.7, 1.5 Hz, 1H), 7.56 (t, J=7.7 Hz, 1H), 7.34 (m, 1H), 7.29 (d, J=7.9 Hz, 1H), 7.14-6.96 (m, 4H), 2.28 (s, 3H), 2.26 (s, 3H)。 Example 19: 3 ′-{N ′-[3- (3,4-dimethyl-phenyl) -4-oxo-2-thioxo-thiazolidine-5-ylidene] -hydrazino} -2′-hydroxy-biphenyl-3 -Carboxylic acid (Compound 119)

This compound was prepared as described in Scheme IV. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 12.83 (s, 1H), 10.76 (s, 1H), 9.35 (s, 1H), 8.15 (t, J = 1.5 Hz, 1H), 7.91 (m, 1H), 7.79 (dt, J = 7.7, 1.5 Hz, 1H), 7.56 (t, J = 7.7 Hz, 1H), 7.34 (m, 1H), 7.29 (d, J = 7.9 Hz, 1H), 7.14- 6.96 (m, 4H), 2.28 (s, 3H), 2.26 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.06 (s, 1H), 9.27 (s, 1H), 8.11 (t, J=1.7 Hz, 1H), 7.94 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.79 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.73 (dd, J=7.7, 1.3 Hz, 1H), 7.73 (dd, J=7.7, 1.6 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.47 (d, J=8.8 Hz, 2H), 7.45 (d, J=8.8 Hz, 2H), 7.29 (td, J=7.7, 1.3 Hz, 1H), 7.19 (td, J=7.7, 0.8 Hz, 1H), 7.11 (t, J=7.7 Hz, 1H), 7.00 (dd, J=7.7, 1.6 Hz, 1H), 6.88 (dd, J=7.7, 0.8 Hz, 1H), 3.00 (７重線(sept), J=6.9 Hz, 1H), 1.27 (d, J=6.9 Hz, 6H)。 Example 20: 2'-Hydroxy-3 '-{N'-[1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3 -Carboxylic acid (compound 120)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.06 (s, 1H), 9.27 (s, 1H), 8.11 (t, J = 1.7 Hz, 1H), 7.94 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.73 (dd, J = 7.7, 1.3 Hz, 1H), 7.73 (dd, J = 7.7, 1.6 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.47 (d, J = 8.8 Hz, 2H), 7.45 (d, J = 8.8 Hz, 2H), 7.29 (td, J = 7.7, 1.3 Hz, 1H), 7.19 (td, J = 7.7, 0.8 Hz, 1H), 7.11 (t, J = 7.7 Hz, 1H), 7.00 (dd, J = 7.7, 1.6 Hz, 1H), 6.88 (dd, J = 7.7, 0.8 Hz, 1H), 3.00 (sept), J = 6.9 Hz, 1H), 1.27 (d, J = 6.9 Hz, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 12.95 (s, 1H), 9.34 (s, 1H), 8.11 (t, J=1.7 Hz, 1H), 8.09 (m, 1H), 7.96 (t, J=8.0 Hz, 1H), 7.94 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.86 (m, 1H), 7.79 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.77 (m, 1H), 7.75 (dd, J=8.0, 1.5 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.32 (td, J=7.6, 1.4 Hz, 1H), 7.24 (td, J=7.6, 0.9 Hz, 1H), 7.13 (t, J=7.7 Hz, 1H), 7.03 (dd, J=7.7, 1.6 Hz, 1H), 6.86 (dm, J=7.6 Hz, 1H)。 Example 21: 3 ′-{N ′-[1- (2-fluoro-4-trifluoromethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ′ -Hydroxy-biphenyl-3-carboxylic acid (Compound 121)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 12.95 (s, 1H), 9.34 (s, 1H), 8.11 (t, J = 1.7 Hz, 1H), 8.09 (m, 1H), 7.96 (t, J = 8.0 Hz, 1H), 7.94 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.86 (m, 1H), 7.79 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.77 (m , 1H), 7.75 (dd, J = 8.0, 1.5 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.32 (td, J = 7.6, 1.4 Hz, 1H), 7.24 (td, J = 7.6, 0.9 Hz, 1H), 7.13 (t, J = 7.7 Hz, 1H), 7.03 (dd, J = 7.7, 1.6 Hz, 1H), 6.86 (dm, J = 7.6 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 12.99 (s, 1H), 9.29 (s, 1H), 8.11 (t, J=1.7 Hz, 1H), 7.94 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.79 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.75-7.72 (m, 2H), 7.59 (t, J=7.7 Hz, 1H), 7.52 (t, J=8.0 Hz, 1H), 7.37 (dd, J=11.3, 1.4 Hz, 1H), 7.29 (td, J=7.7, 1.2 Hz, 1H), 7.25 (dm, J=8.0 Hz, 1H), 7.21 (td, J=7.7, 1.0 Hz, 1H) 7.12 (t, J=7.7 Hz, 1H), 7.01 (dd, J=7.7, 1.6 Hz, 1H), 6.71 (dm, J=7.7 Hz, 1H), 2.43 (s, 3H)。 Example 22: 3 ′-{N ′-[1- (2-Fluoro-4-methyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy -Biphenyl-3-carboxylic acid (Compound 122)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 12.99 (s, 1H), 9.29 (s, 1H), 8.11 (t, J = 1.7 Hz, 1H), 7.94 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.75-7.72 (m, 2H), 7.59 (t, J = 7.7 Hz, 1H), 7.52 (t, J = 8.0 Hz , 1H), 7.37 (dd, J = 11.3, 1.4 Hz, 1H), 7.29 (td, J = 7.7, 1.2 Hz, 1H), 7.25 (dm, J = 8.0 Hz, 1H), 7.21 (td, J = 7.7, 1.0 Hz, 1H) 7.12 (t, J = 7.7 Hz, 1H), 7.01 (dd, J = 7.7, 1.6 Hz, 1H), 6.71 (dm, J = 7.7 Hz, 1H), 2.43 (s, 3H ).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 12.99 (s, 1H), 9.32 (s, 1H), 8.12 (m, 2H), 7.98 (d, J=8.7 Hz, 1H), 7.94 (dd, J=8.7, 2.2 Hz, 1H), 7.94 (m, 1H), 7.79 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.76 (dd, J=7.6, 1.0 Hz, 1H), 7.74 (dd, J=7.9, 1.6 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.32 (td, J=7.6, 1.4 Hz, 1H), 7.23 (td, J=7.6, 1.0 Hz, 1H), 7.12 (t, J=7.9 Hz, 1H), 7.03-7.00 (m, 2H)。 Example 23: 3 '-{N'-[1- (4-Chloro-3-trifluoromethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid (Compound 123)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 12.99 (s, 1H), 9.32 (s, 1H), 8.12 (m, 2H), 7.98 (d, J = 8.7 Hz, 1H), 7.94 (dd, J = 8.7, 2.2 Hz, 1H), 7.94 (m, 1H), 7.79 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.76 (dd, J = 7.6, 1.0 Hz, 1H), 7.74 (dd , J = 7.9, 1.6 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.32 (td, J = 7.6, 1.4 Hz, 1H), 7.23 (td, J = 7.6, 1.0 Hz, 1H) , 7.12 (t, J = 7.9 Hz, 1H), 7.03-7.00 (m, 2H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.22 (s, 1H), 8.19 (t, J=1.6 Hz, 1H), 8.03 (dt, J=7.8, 1.6 Hz, 1H), 7.79 (dt, J=7.8, 1.6 Hz, 1H), 7.78 (dd, J=7.8, 1.6 Hz, 1H), 7.76 (dd, J=7.7, 1.0 Hz, 1H), 7.60 (t, J=7.8 Hz, 1H), 7.46 (d, J=8.4 Hz, 2H), 7.44 (d, J=8.4 Hz, 2H), 7.29 (td, J=7.7, 1.0 Hz, 1H), 7.19 (td, J=7.7, 1.0 Hz, 1H), 7.12 (t, J=7.8 Hz, 1H), 7.01 (dd, J=7.8, 1.6 Hz, 1H), 6.92 (d, J=7.7, 1.0 Hz, 1H), 2.72 (t, J=7.5 Hz, 2H), 1.67 (m, 2H), 1.40 (m, 2H), 0.95 (t, J=7.5 Hz, 3H)。 Example 24: 3 ′-{N ′-[1- (4-Butyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy-biphenyl-3 -Carboxylic acid (Compound 124)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.22 (s, 1H), 8.19 (t, J = 1.6 Hz, 1H), 8.03 (dt, J = 7.8, 1.6 Hz, 1H), 7.79 (dt, J = 7.8, 1.6 Hz, 1H), 7.78 (dd, J = 7.8, 1.6 Hz, 1H), 7.76 (dd, J = 7.7, 1.0 Hz, 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.46 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H), 7.29 (td, J = 7.7, 1.0 Hz, 1H), 7.19 (td, J = 7.7, 1.0 Hz, 1H ), 7.12 (t, J = 7.8 Hz, 1H), 7.01 (dd, J = 7.8, 1.6 Hz, 1H), 6.92 (d, J = 7.7, 1.0 Hz, 1H), 2.72 (t, J = 7.5 Hz , 2H), 1.67 (m, 2H), 1.40 (m, 2H), 0.95 (t, J = 7.5 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.03 (s, 1H), 9.31 (s, 1H), 8.12 (t, J=1.6 Hz, 1H), 7.94 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.79 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.74 (ddd, J=7.6, 1.2, 0.6 Hz, 1H), 7.73 (dd, J=7.7, 1.6 Hz, 1H), 7.65 (ddd, J=8.5, 8.0, 6.6 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.49 (ddd, J=9.9, 2.6, 2.0 Hz, 1H) 7.42 (ddd, J=8.0, 2.0, 0.8 Hz, 1H), 7.36 (tdd, J=8.5, 2.6, 0.8 Hz, 1H), 7.31 (td, J=7.6, 1.2 Hz, 1H), 7.21 (td, J=7.6, 0.8 Hz, 1H), 7.11 (t, J=7.7 Hz, 1H), 7.01 (dd, J=7.7, 1.6 Hz, 1H), 6.96 (ddd, J=7.6, 0.8, 0.6 Hz, 1H)。 Example 25: 3 ′-{N ′-[1- (3-Fluoro-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy-biphenyl-3 -Carboxylic acid (Compound 125)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.03 (s, 1H), 9.31 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.74 (ddd, J = 7.6, 1.2, 0.6 Hz, 1H), 7.73 (dd, J = 7.7, 1.6 Hz, 1H) , 7.65 (ddd, J = 8.5, 8.0, 6.6 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.49 (ddd, J = 9.9, 2.6, 2.0 Hz, 1H) 7.42 (ddd, J = 8.0, 2.0, 0.8 Hz, 1H), 7.36 (tdd, J = 8.5, 2.6, 0.8 Hz, 1H), 7.31 (td, J = 7.6, 1.2 Hz, 1H), 7.21 (td, J = 7.6, 0.8 Hz , 1H), 7.11 (t, J = 7.7 Hz, 1H), 7.01 (dd, J = 7.7, 1.6 Hz, 1H), 6.96 (ddd, J = 7.6, 0.8, 0.6 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.22 (s, 1H), 8.20 (t, J=1.6 Hz, 1H), 8.03 (dt, J=7.8, 1.6 Hz, 1H), 7.80-7.77 (m, 2H), 7.76 (dd, J=7.7, 1.0 Hz, 1H), 7.60 (t, J=7.8 Hz, 1H), 7.48 (t, J=7.8 Hz, 1H), 7.38 (t, J=1.6 Hz, 1H), 7.35 (m, 1H), 7.30 (m, 1H), 7.29 (td, J=7.7, 1.0 Hz, 1H), 7.19 (td, J=7.7, 1.0 Hz, 1H), 7.12 (t, J=7.8 Hz, 1H), 7.01 (dd, J=7.8, 1.7 Hz, 1H), 6.93 (dd, J=7.7, 1.0 Hz, 1H), 2.44 (s, 3H)。 Example 26: 2'-hydroxy-3 '-[N'-(2-oxo-1-m-tolyl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid ( Compound 126)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.22 (s, 1H), 8.20 (t, J = 1.6 Hz, 1H), 8.03 (dt, J = 7.8, 1.6 Hz, 1H), 7.80-7.77 ( m, 2H), 7.76 (dd, J = 7.7, 1.0 Hz, 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.48 (t, J = 7.8 Hz, 1H), 7.38 (t, J = 1.6 Hz, 1H), 7.35 (m, 1H), 7.30 (m, 1H), 7.29 (td, J = 7.7, 1.0 Hz, 1H), 7.19 (td, J = 7.7, 1.0 Hz, 1H), 7.12 (t , J = 7.8 Hz, 1H), 7.01 (dd, J = 7.8, 1.7 Hz, 1H), 6.93 (dd, J = 7.7, 1.0 Hz, 1H), 2.44 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.04 (s, 1H), 9.28 (s, 1H), 8.11 (t, J=1.6 Hz, 1H), 7.94 (dt, J=7.9, 1.6 Hz, 1H), 7.78 (dt, J=7.9, 1.6 Hz, 1H), 7.74 (dd, J=7.8, 1.0 Hz, 1H), 7.73 (dd, J=7.9, 1.6 Hz, 1H), 7.63-7.57 (m, 3H), 7.44 (t, J=8.6 Hz, 2H), 7.29 (td, J=7.8, 1.0 Hz, 1H), 7.20 (td, J=7.8, 1.0 Hz, 1H), 7.11 (t, J=7.9 Hz, 1H), 7.00 (dd, J=7.9, 1.6 Hz, 1H), 6.86 (d, J=7.8 Hz, 1H)。 Example 27: 3 ′-{N ′-[1- (4-Fluoro-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy-biphenyl-3 -Carboxylic acid (Compound 127)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.04 (s, 1H), 9.28 (s, 1H), 8.11 (t, J = 1.6 Hz, 1H), 7.94 (dt, J = 7.9, 1.6 Hz, 1H), 7.78 (dt, J = 7.9, 1.6 Hz, 1H), 7.74 (dd, J = 7.8, 1.0 Hz, 1H), 7.73 (dd, J = 7.9, 1.6 Hz, 1H), 7.63-7.57 (m , 3H), 7.44 (t, J = 8.6 Hz, 2H), 7.29 (td, J = 7.8, 1.0 Hz, 1H), 7.20 (td, J = 7.8, 1.0 Hz, 1H), 7.11 (t, J = 7.9 Hz, 1H), 7.00 (dd, J = 7.9, 1.6 Hz, 1H), 6.86 (d, J = 7.8 Hz, 1H).

この化合物は、反応式ＩＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.10 (s, 1H), 9.27 (s, 1H), 8.13 (s, 1H), 7.95 (d, J = 7.5 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.74 (d, J = 6.5 Hz, 1H), 7.60 (t, J = 7.5 Hz, 1H), 7.36-7.32 (m, 4H), 7.28-7.25 (m, 1H), 7.24 (d, J = 2.5 Hz, 1H), 7.11 (t, J = 7.5 Hz, 1H), 7.00 (d, J = 8.0 Hz, 1H), 6.97 (d, J = 8.5 Hz, 1H), 6.84 (dd, J = 2.5, 9.0 Hz, 1H), 5.01 (s, 2H), 3.79 (s, 3H)。 Example 28: 3 ′-[N ′-(1-Benzyl-5-methoxy-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2′-hydroxy-biphenyl-3-carboxylic acid Acid (Compound 128)

This compound was prepared as described in Scheme III. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.10 (s, 1H), 9.27 (s, 1H), 8.13 (s, 1H), 7.95 (d, J = 7.5 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.74 (d, J = 6.5 Hz, 1H), 7.60 (t, J = 7.5 Hz, 1H), 7.36-7.32 (m, 4H), 7.28-7.25 (m, 1H), 7.24 (d, J = 2.5 Hz, 1H), 7.11 (t, J = 7.5 Hz, 1H), 7.00 (d, J = 8.0 Hz, 1H), 6.97 (d, J = 8.5 Hz, 1H), 6.84 ( dd, J = 2.5, 9.0 Hz, 1H), 5.01 (s, 2H), 3.79 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.03 (s, 1H), 9.32 (s, 1H), 8.12 (s, 1H), 7.99 (s, 1H), 7.95-7.91 (m, 4 H), 7.81-7.73 (m, 3H), 7.60 (t, J = 7.5 Hz, 1H), 7.32 (t, J = 7.5 Hz, 1H), 7.23 (t, J = 7.5 Hz, 1H), 7.12 (t, J = 7.5 Hz, 1H), 7.02 (dd, J = 1.5, 7.5 Hz, 1H), 6.95 (d, J = 7.5 Hz, 1H)。 Example 29: 2'-hydroxy-3 '-{N'-[2-oxo-1- (3-trifluoromethyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl -3-carboxylic acid (compound 129)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.03 (s, 1H), 9.32 (s, 1H), 8.12 (s, 1H), 7.99 (s, 1H), 7.95-7.91 (m, 4 H) , 7.81-7.73 (m, 3H), 7.60 (t, J = 7.5 Hz, 1H), 7.32 (t, J = 7.5 Hz, 1H), 7.23 (t, J = 7.5 Hz, 1H), 7.12 (t, J = 7.5 Hz, 1H), 7.02 (dd, J = 1.5, 7.5 Hz, 1H), 6.95 (d, J = 7.5 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.09 (s, 2H), 9.35 (s, 1H), 8.11 (d, J=1.5 Hz, 1H), 7.94 (d, J=7.8 Hz, 1H), 7.79 (d, J=8.3 Hz, 2H), 7.76 (d, J=2.0 Hz, 1H), 7.60 (t, 1H), 7.46 (q, J=6.0 Hz, 4H), 7.30 (dd, J=8.3, 2.4 Hz, 1H), 7.12 (t, J=7.8 Hz, 1H), 7.03 (dd, J=7.8, 1.5 Hz, 1H), 6.88 (d, J=8.8 Hz, 1H), 3.00 (sept, J=7.0 Hz, 1H), 1.27 (d, J=6.8 Hz, 8H)。 Example 30: 3 ′-{N ′-[5-chloro-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy -Biphenyl-3-carboxylic acid (Compound 130)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.09 (s, 2H), 9.35 (s, 1H), 8.11 (d, J = 1.5 Hz, 1H), 7.94 (d, J = 7.8 Hz, 1H) , 7.79 (d, J = 8.3 Hz, 2H), 7.76 (d, J = 2.0 Hz, 1H), 7.60 (t, 1H), 7.46 (q, J = 6.0 Hz, 4H), 7.30 (dd, J = 8.3, 2.4 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 7.03 (dd, J = 7.8, 1.5 Hz, 1H), 6.88 (d, J = 8.8 Hz, 1H), 3.00 (sept, J = 7.0 Hz, 1H), 1.27 (d, J = 6.8 Hz, 8H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.05 (s, 1H), 9.30 (s, 1H), 8.11 (t, J=1.5 Hz, 1H), 7.94 (qn, J=2.3 Hz, 1H), 7.79 (dt, J=7.8, 1.5 Hz, 1H), 7.73 (dd, J=7.8, 1.5 Hz, 2H), 7.59 (t, J=7.8 Hz, 1H), 7.48 (m, 4H), 7.24 (dd, J=8.1, 1.7 Hz, 1H), 7.11 (t, 1H), 7.02 (dd, J=7.6, 1.7 Hz, 1H), 6.82 (d, J=1.5 Hz, 1H), 3.00 (sept, J=6.8 Hz, 1H), 1.27 (d, J=6.8 Hz, 6H)。 Example 31: 3 ′-{N ′-[6-chloro-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy -Biphenyl-3-carboxylic acid (Compound 131)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.05 (s, 1H), 9.30 (s, 1H), 8.11 (t, J = 1.5 Hz, 1H), 7.94 (qn, J = 2.3 Hz, 1H) , 7.79 (dt, J = 7.8, 1.5 Hz, 1H), 7.73 (dd, J = 7.8, 1.5 Hz, 2H), 7.59 (t, J = 7.8 Hz, 1H), 7.48 (m, 4H), 7.24 ( dd, J = 8.1, 1.7 Hz, 1H), 7.11 (t, 1H), 7.02 (dd, J = 7.6, 1.7 Hz, 1H), 6.82 (d, J = 1.5 Hz, 1H), 3.00 (sept, J = 6.8 Hz, 1H), 1.27 (d, J = 6.8 Hz, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.12 (s, 1H), 13.04 (s, 1H), 9.34 (s, 1H), 8.11 (t, 1H), 7.94 (t, 1H), 7.78 (dt, J=9.1, 5.2 Hz, 2H), 7.58 (m, 2H), 7.46 (m, 4H), 7.09-7.09 (m, 2H), 7.03 (dd, J=7.8, 2.0 Hz, 1H), 6.87 (dd, J=8.8, 3.9 Hz, 1H), 3.00 (sept, J=7.0 Hz, 1H), 1.27 (d, J=6.8 Hz, 6H)。 Example 32: 3 ′-{N ′-[5-Fluoro-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy -Biphenyl-3-carboxylic acid (Compound 132)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.12 (s, 1H), 13.04 (s, 1H), 9.34 (s, 1H), 8.11 (t, 1H), 7.94 (t, 1H), 7.78 ( dt, J = 9.1, 5.2 Hz, 2H), 7.58 (m, 2H), 7.46 (m, 4H), 7.09-7.09 (m, 2H), 7.03 (dd, J = 7.8, 2.0 Hz, 1H), 6.87 (dd, J = 8.8, 3.9 Hz, 1H), 3.00 (sept, J = 7.0 Hz, 1H), 1.27 (d, J = 6.8 Hz, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.09 (s, 1H), 13.03 (s, 1H), 9.26 (s, 1H), 8.11 (t, J=1.5 Hz, 1H), 7.94 (d, J=7.8 Hz, 1H), 7.78 (dt, J=9.9, 5.5 Hz, 2H), 7.60 (t, J=7.8 Hz, 1H), 7.45 (q, J=5.4 Hz, 4H), 7.32 (d, J=2.4 Hz, 1H), 7.11 (t, 1H), 7.00 (dd, J=7.6, 1.7 Hz, 1H), 6.86 (dd, J=8.5, 2.7 Hz, 1H), 6.82 (d, J=8.8 Hz, 1H), 3.83 (s,3H), 3.00 (sept, J=6.8 Hz, 1H), 1.27 (d, J=6.8 Hz, 6H)。 Example 33: 3 ′-{N ′-[5-methoxy-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy -Biphenyl-3-carboxylic acid (Compound 133)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.09 (s, 1H), 13.03 (s, 1H), 9.26 (s, 1H), 8.11 (t, J = 1.5 Hz, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.78 (dt, J = 9.9, 5.5 Hz, 2H), 7.60 (t, J = 7.8 Hz, 1H), 7.45 (q, J = 5.4 Hz, 4H), 7.32 (d, J = 2.4 Hz, 1H), 7.11 (t, 1H), 7.00 (dd, J = 7.6, 1.7 Hz, 1H), 6.86 (dd, J = 8.5, 2.7 Hz, 1H), 6.82 (d, J = 8.8 Hz, 1H), 3.83 (s, 3H), 3.00 (sept, J = 6.8 Hz, 1H), 1.27 (d, J = 6.8 Hz, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.13 (s, 1H), 13.03 (s, 1H), 9.33 (s, 1H), 8.12 (t, 1H), 7.94 (d, J=7.8 Hz, 1H), 7.79 (dt, J=4.8, 3.8 Hz, 2H), 7.60 (t, J=7.8 Hz, 1H), 7.56 (dd, J=8.1, 2.7 Hz, 1H), 7.35 (d, J=8.3 Hz, 1H), 7.30 (d, J=2.0 Hz, 1H), 7.23 (dd, J=8.1, 2.2 Hz, 1H), 7.14-7.08 (m, 2H), 7.03 (dd, J=7.8, 1.5 Hz, 1H), 6.85 (q, J=4.2 Hz, 1H), 2.31 (s, 3H), 2.30 (s, 3H)。 Example 34: 3 '-{N'-[1- (3,4-dimethyl-phenyl) -5-fluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid (Compound 134)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.13 (s, 1H), 13.03 (s, 1H), 9.33 (s, 1H), 8.12 (t, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.79 (dt, J = 4.8, 3.8 Hz, 2H), 7.60 (t, J = 7.8 Hz, 1H), 7.56 (dd, J = 8.1, 2.7 Hz, 1H), 7.35 (d, J = 8.3 Hz, 1H), 7.30 (d, J = 2.0 Hz, 1H), 7.23 (dd, J = 8.1, 2.2 Hz, 1H), 7.14-7.08 (m, 2H), 7.03 (dd, J = 7.8, 1.5 Hz , 1H), 6.85 (q, J = 4.2 Hz, 1H), 2.31 (s, 3H), 2.30 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.03 (s, 1H), 13.00 (s, 1H), 9.31 (s, 1H), 8.12 (t, J=1.6 Hz, 1H), 8.06 (dd, J=6.6, 2.7 Hz, 1H), 7.99 (dd, J=8.8, 4.4, 2.7 Hz, 1H), 7.94 (ddd, J=7.8, 1.6, 1.3 Hz, 1H), 7.80-7.72 (m, 4H), 7.60 (t, J=7.8 Hz, 1H), 7.31 (td, J=7.7, 1.3 Hz, 1H), 7.22 (td, J=7.7, 1.0 Hz, 1H), 7.12 (t, J=7.8 Hz, 1H), 7.01 (dd, J=7.8, 1.6 Hz, 1H), 6.94 (ddd, J=7.7, 1.0, 0.6 Hz, 1H)。 Example 35: 3 ′-{N ′-[1- (4-Fluoro-3-trifluoromethyl-phenyl) -5-fluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino } -2'-Hydroxy-biphenyl-3-carboxylic acid (Compound 135)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.03 (s, 1H), 13.00 (s, 1H), 9.31 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 8.06 (dd, J = 6.6, 2.7 Hz, 1H), 7.99 (dd, J = 8.8, 4.4, 2.7 Hz, 1H), 7.94 (ddd, J = 7.8, 1.6, 1.3 Hz, 1H), 7.80-7.72 (m, 4H) , 7.60 (t, J = 7.8 Hz, 1H), 7.31 (td, J = 7.7, 1.3 Hz, 1H), 7.22 (td, J = 7.7, 1.0 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 7.01 (dd, J = 7.8, 1.6 Hz, 1H), 6.94 (ddd, J = 7.7, 1.0, 0.6 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.02 (s, 1H), 12.99 (s, 1H), 9.33 (s, 1H), 8.12 (t, J=1.6 Hz, 1H), 7.94 (ddd, J=7.7, 1.6, 1.1 Hz, 1H), 7.80 (ddd, J=7.7, 1.6, 1.1 Hz, 1H), 7.78 (t, J=1.9 Hz, 1H), 7.76-7.72 (m, 4H), 7.60 (t, J=7.7 Hz, 1H), 7.32 (td, J=7.6, 1.2 Hz, 1H), 7.23 (td, J=7.6, 0.7 Hz, 1H), 7.12 (t, J=7.8 Hz, 1H), 7.01 (dd, J=7.8, 1.7 Hz, 1H), 7.00 (d, J=7.6 Hz, 1H)。 Example 36: 3 '-{N'-[1- (3,5-dichloro-phenyl) -5-fluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid (Compound 136)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.02 (s, 1H), 12.99 (s, 1H), 9.33 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.1 Hz, 1H), 7.80 (ddd, J = 7.7, 1.6, 1.1 Hz, 1H), 7.78 (t, J = 1.9 Hz, 1H), 7.76-7.72 (m, 4H), 7.60 (t, J = 7.7 Hz, 1H), 7.32 (td, J = 7.6, 1.2 Hz, 1H), 7.23 (td, J = 7.6, 0.7 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H) , 7.01 (dd, J = 7.8, 1.7 Hz, 1H), 7.00 (d, J = 7.6 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.05 (s, 1H), 13.02 (s, 1H), 9.32 (s, 1H), 8.11 (t, J=1.7 Hz, 1H), 7.94 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.79 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.73 (dd, J=8.0, 1.8 Hz, 1H), 7.73 (d, J=8.0 Hz, 1H), 7.59 (t, J=7.7 Hz, 1H), 7.45 (d, J=8.6 Hz, 2H), 7.42 (d, J=8.6 Hz, 2H), 7.23 (dd, J=8.0, 1.9 Hz, 1H), 7.11 (dd, J=7.7, 8.0 Hz, 1H), 7.02 (dd, J=7.7, 1.8 Hz, 1H), 6.81 (d, J=1.9 Hz, 1H), 2.66 (t, J=7.4 Hz, 2H), 1.66 (sext, J=7.4 Hz, 2H), 0.95 (t, J=7.4 Hz, 3H)。 Example 37: 3 ′-{N ′-[1- (4-propyl-phenyl) -6-chloro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy -Biphenyl-3-carboxylic acid (Compound 137)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.05 (s, 1H), 13.02 (s, 1H), 9.32 (s, 1H), 8.11 (t, J = 1.7 Hz, 1H), 7.94 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.73 (dd, J = 8.0, 1.8 Hz, 1H), 7.73 (d, J = 8.0 Hz , 1H), 7.59 (t, J = 7.7 Hz, 1H), 7.45 (d, J = 8.6 Hz, 2H), 7.42 (d, J = 8.6 Hz, 2H), 7.23 (dd, J = 8.0, 1.9 Hz , 1H), 7.11 (dd, J = 7.7, 8.0 Hz, 1H), 7.02 (dd, J = 7.7, 1.8 Hz, 1H), 6.81 (d, J = 1.9 Hz, 1H), 2.66 (t, J = 7.4 Hz, 2H), 1.66 (sext, J = 7.4 Hz, 2H), 0.95 (t, J = 7.4 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.05 (s, 1H), 13.03 (s, 1H), 9.29 (s, 1H), 8.12 (s, 1H), 7.94 (d, J=7.8 Hz, 1H), 7.79 (d, J=7.8 Hz, 1H), 7.76-7.70 (m, 4H), 7.62-7.59 (m, 3H), 7.30 (t, J=7.6 Hz, 1H), 7.21 (t, J=7.6 Hz, 1H), 7.12 (t, J=7.9 Hz, 1H), 7.02-6.99 (m, 2H), 6.93 (d, J=7.8 Hz, 1H), 5.32 (m, 1H), 3.17 (d, J=5.3 Hz, 1H)。 Example 38: (±) -2′-hydroxy-3 ′-(N ′-{2-oxo-1- [4- (2,2,2-trifluoro-1-hydroxy-ethyl) -phenyl]- 1,2-dihydro-indole-3-ylidene} -hydrazino) -biphenyl-3-carboxylic acid (compound 138)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.05 (s, 1H), 13.03 (s, 1H), 9.29 (s, 1H), 8.12 (s, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.79 (d, J = 7.8 Hz, 1H), 7.76-7.70 (m, 4H), 7.62-7.59 (m, 3H), 7.30 (t, J = 7.6 Hz, 1H), 7.21 (t, J = 7.6 Hz, 1H), 7.12 (t, J = 7.9 Hz, 1H), 7.02-6.99 (m, 2H), 6.93 (d, J = 7.8 Hz, 1H), 5.32 (m, 1H), 3.17 (d , J = 5.3 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.06 (s, 1H), 13.03 (s, 1H), 9.30 (s, 1H), 8.12 (s, 1H), 7.94 (d, J=7.0 Hz, 1H), 7.79 (d, J=7.0 Hz, 1H), 7.75 (m, 2H), 7.68 (m, 4H), 7.60 (t, J=7.0 Hz, 1H), 7.31 (t, J=7.4 Hz, 1H), 7.22 (t, J=7.4 Hz, 1H), 7.12 (t, J=7.6 Hz, 1H), 7.01 (d, J=7.6 Hz, 1H), 6.97 (m, 1H), 5.22 (q, J=6.7 Hz, 1H), 3.42 (s, 3H)。 Example 39: (±) -2'-hydroxy-3 '-(N'-{2-oxo-1- [4- (2,2,2-trifluoro-1-methoxy-ethyl) -phenyl]- 1,2-Dihydro-indole-3-ylidene} -hydrazino) -biphenyl-3-carboxylic acid (Compound 139)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.06 (s, 1H), 13.03 (s, 1H), 9.30 (s, 1H), 8.12 (s, 1H), 7.94 (d, J = 7.0 Hz, 1H), 7.79 (d, J = 7.0 Hz, 1H), 7.75 (m, 2H), 7.68 (m, 4H), 7.60 (t, J = 7.0 Hz, 1H), 7.31 (t, J = 7.4 Hz, 1H), 7.22 (t, J = 7.4 Hz, 1H), 7.12 (t, J = 7.6 Hz, 1H), 7.01 (d, J = 7.6 Hz, 1H), 6.97 (m, 1H), 5.22 (q, J = 6.7 Hz, 1H), 3.42 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.05 (s, 1H), 13.02 (s, 1H), 9.28 (s, 1H), 8.12 (t, J=1.7 Hz, 1H), 7.94 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.79 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.74 (m, 2H), 7.62-7.56 (m, 5H), 7.30 (td, J=7.6, 1.2 Hz, 1H), 7.21 (td, J=7.6, 0.8 Hz, 1H), 7.12 (t, J=7.8 Hz, 1H), 7.01 (dd, J=7.8, 1.6 Hz, 1H), 6.92 (d, J=7.8, 1H), 3.79 (q, J=11.5 Hz, 2H)。 Example 40: 2′-hydroxy-3 ′-(N ′-{2-oxo-1- [4- (2,2,2-trifluoro-ethyl) -phenyl] -1,2-dihydro-indole- 3-Ilidene} -hydrazino) -biphenyl-3-carboxylic acid (Compound 140)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.05 (s, 1H), 13.02 (s, 1H), 9.28 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 7.94 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.74 (m, 2H), 7.62-7.56 (m, 5H), 7.30 (td, J = 7.6, 1.2 Hz, 1H), 7.21 (td, J = 7.6, 0.8 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 7.01 (dd, J = 7.8, 1.6 Hz, 1H), 6.92 ( d, J = 7.8, 1H), 3.79 (q, J = 11.5 Hz, 2H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, CD₃OD) δ 8.17 (s, 1H), 8.00 (d, J=7.7 Hz, 1H), 7.74 (d, J=7.7 Hz, 1H), 7.65 (d, J=7.7 Hz, 1H), 7.54 (t, J=7.7 Hz, 1H), 7.32 (d, J=7.7 Hz, 1H), 7.21 (s, 1H), 7.15 (d, J=7.7 Hz, 1H), 7.08 (t, J=7.7 Hz, 1H), 7.02 (m, 1H), 6.95 (d, J=7.7 Hz, 1H), 6.57 (m, 1H), 2.72 (s, 3H), 2.35 (s, 3H), 2.34 (s, 3H), 2.33 (s, 3H)。 Example 41: 3 '-{N'-[1- (3,4-dimethyl-phenyl) -4,5-dimethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 141)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, CD ₃ OD) δ 8.17 (s, 1H), 8.00 (d, J = 7.7 Hz, 1H), 7.74 (d, J = 7.7 Hz, 1H), 7.65 (d, J = 7.7 Hz, 1H), 7.54 (t, J = 7.7 Hz, 1H), 7.32 (d, J = 7.7 Hz, 1H), 7.21 (s, 1H), 7.15 (d, J = 7.7 Hz, 1H), 7.08 ( t, J = 7.7 Hz, 1H), 7.02 (m, 1H), 6.95 (d, J = 7.7 Hz, 1H), 6.57 (m, 1H), 2.72 (s, 3H), 2.35 (s, 3H), 2.34 (s, 3H), 2.33 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.29 (s, 1H), 8.11 (s, 1H), 7.91 (d, J=7.3 Hz, 1H), 7.74 (d, J=7.3 Hz, 1H), 7.61 (d, J=7.8 Hz, 1H), 7.54 (t, J=7.3 Hz, 1H), 7.35 (d, J=8.0 Hz, 1H), 7.28 (s, 1H), 7.21 (dd, J=8.0, 1.7 Hz, 1H), 7.10 (m, 1H), 7.06 (t, J=9.3 Hz, 1H), 7.01 (d, J=7.8 Hz, 1H), 6.65 (dd, J=8.6, 3.8 Hz, 1H), 2.63 (br s, 3H), 2.31 (s, 3H), 2.30 (s, 3H)。 Example 42: 3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -5-fluoro-4-methyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino } -2'-Hydroxy-biphenyl-3-carboxylic acid (Compound 142)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.29 (s, 1H), 8.11 (s, 1H), 7.91 (d, J = 7.3 Hz, 1H), 7.74 (d, J = 7.3 Hz, 1H) , 7.61 (d, J = 7.8 Hz, 1H), 7.54 (t, J = 7.3 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 7.28 (s, 1H), 7.21 (dd, J = 8.0, 1.7 Hz, 1H), 7.10 (m, 1H), 7.06 (t, J = 9.3 Hz, 1H), 7.01 (d, J = 7.8 Hz, 1H), 6.65 (dd, J = 8.6, 3.8 Hz, 1H), 2.63 (br s, 3H), 2.31 (s, 3H), 2.30 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300 MHz, DMSO-d₆) δ 9.28 (s, 1H), 8.11 (t, J=1.6 Hz, 1H), 7.94 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.79 (ddd, J=7.6, 1.6, 1.2 Hz, 1H), 7.74 (dd, J=7.9, 1.6 Hz, 1H), 7.59 (t, J=7.7 Hz, 1H), 7.49 (d, J=9.0 Hz, 1H), 7.35 (d, J=8.0 Hz, 1H), 7.28 (d, J=2.1 Hz, 1H), 7.22 (dd, J=8.0, 2.1 Hz, 1H), 7.11 (t, J=7.9 Hz, 1H), 7.01 (dd, J=7.9, 1.6 Hz, 1H), 6.74 (d, J=5.8 Hz, 1H), 2.31 (s, 3H), 2.30 (s, 3H), 2.24 (d, J=1.8 Hz, 3H)。 Example 43: 3 '-{N'-[1- (3,4-dimethyl-phenyl) -5-fluoro-6-methyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino } -2'-Hydroxy-biphenyl-3-carboxylic acid (Compound 143)

This compound was prepared as described in Scheme II. ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 9.28 (s, 1H), 8.11 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.79 ( ddd, J = 7.6, 1.6, 1.2 Hz, 1H), 7.74 (dd, J = 7.9, 1.6 Hz, 1H), 7.59 (t, J = 7.7 Hz, 1H), 7.49 (d, J = 9.0 Hz, 1H ), 7.35 (d, J = 8.0 Hz, 1H), 7.28 (d, J = 2.1 Hz, 1H), 7.22 (dd, J = 8.0, 2.1 Hz, 1H), 7.11 (t, J = 7.9 Hz, 1H ), 7.01 (dd, J = 7.9, 1.6 Hz, 1H), 6.74 (d, J = 5.8 Hz, 1H), 2.31 (s, 3H), 2.30 (s, 3H), 2.24 (d, J = 1.8 Hz , 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.13 (s, 1H), 12.57 (s, 1H), 10.88 (s, 1H), 7.92 (d, J=7.9 Hz, 1H), 7.82 (d, J=8.4 Hz, 1H), 7.70 (s, 1H), 7.55 (d, J=8.1 Hz, 1H), 7.39 (d, J=7.9 Hz, 1H), 7.33 (br s, 1H), 7.28-7.24 (m, 2H), 7.16 (br s, 1H), 6.96 (s, 1H), 2.33 (s, 3H), 2.31 (s, 3H)。 Example 44: 5- (4- {N '-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino } -3-Hydroxy-benzylidene) -thiazolidine-2,4-dione (compound 144)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.13 (s, 1H), 12.57 (s, 1H), 10.88 (s, 1H), 7.92 (d, J = 7.9 Hz, 1H), 7.82 (d, J = 8.4 Hz, 1H), 7.70 (s, 1H), 7.55 (d, J = 8.1 Hz, 1H), 7.39 (d, J = 7.9 Hz, 1H), 7.33 (br s, 1H), 7.28-7.24 (m, 2H), 7.16 (br s, 1H), 6.96 (s, 1H), 2.33 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.00 (s, 1H), 12.54 (s, 1H), 10.74 (s, 1H), 7.76 (d, J=8.3 Hz, 1H), 7.72 (d, J=7.5 Hz, 1H), 7.68 (s, 1H), 7.36 (d, J=8.3 Hz, 1H), 7.32-7.29 (m, 2H), 7.25-7.22 (m, 2H), 7.19 (t, J=7.5, 1H), 7.15 (d, J=1.8 Hz, 1H), 6.86 (d, J=7.5 Hz, 1H), 2.32 (s, 3H), 2.31 (s, 3H)。 Example 45: 5- (4- {N '-[1- (3,4-dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -3-hydroxy- Benzylidene) -thiazolidine-2,4-dione (Compound 145)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.00 (s, 1H), 12.54 (s, 1H), 10.74 (s, 1H), 7.76 (d, J = 8.3 Hz, 1H), 7.72 (d, J = 7.5 Hz, 1H), 7.68 (s, 1H), 7.36 (d, J = 8.3 Hz, 1H), 7.32-7.29 (m, 2H), 7.25-7.22 (m, 2H), 7.19 (t, J = 7.5, 1H), 7.15 (d, J = 1.8 Hz, 1H), 6.86 (d, J = 7.5 Hz, 1H), 2.32 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.37 (s, 1H), 13.05 (s, 1H), 9.49 (s, 1H), 8.12 (t, J=1.6 Hz, 1H), 7.95 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.80 (ddd, J=7.7, 1.6, 1.3 Hz, 1H), 7.67 (dd, J=7.9, 1.6 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.50 (d, J=9.5 Hz, 1H), 7.39 (d, J=8.0 Hz, 1H), 7.32 (d, J=2.1 Hz, 1H), 7.26 (dd, J=8.0, 2.1 Hz, 1H), 7.15 (t, J=7.9 Hz, 1H), 7.08 (dd, J=7.9, 1.6 Hz, 1H), 6.81 (s, 1H), 2.32 (s, 3H), 2.31 (s, 3H)。 Example 46: 3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -Hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 146)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.37 (s, 1H), 13.05 (s, 1H), 9.49 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.95 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.80 (ddd, J = 7.7, 1.6, 1.3 Hz, 1H), 7.67 (dd, J = 7.9, 1.6 Hz, 1H), 7.60 (t, J = 7.7 Hz , 1H), 7.50 (d, J = 9.5 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.32 (d, J = 2.1 Hz, 1H), 7.26 (dd, J = 8.0, 2.1 Hz , 1H), 7.15 (t, J = 7.9 Hz, 1H), 7.08 (dd, J = 7.9, 1.6 Hz, 1H), 6.81 (s, 1H), 2.32 (s, 3H), 2.31 (s, 3H) .

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.45 (s, 1H), 13.06 (s, 1H), 9.51 (s, 1H), 8.12 (t, J=1.6 Hz, 1H), 7.95 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.80 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.74 (dd, J=7.8, 1.5 Hz, 1H), 7.62 (m, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.39 (d, J=8.2 Hz, 1H), 7.32 (d, J=2.1 Hz, 1H), 7.26 (dd, J=8.2, 2.1 Hz, 1H), 7.16 (t, J=7.8 Hz, 1H), 7.09 (dd, J=7.8, 1.5 Hz, 1H), 6.89 (m, 1H), 2.32 (s, 3H), 2.31 (s, 3H)。 Example 47: 3 ′-{N ′-[4-chloro-1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -Hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 147)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.45 (s, 1H), 13.06 (s, 1H), 9.51 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.95 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.80 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.74 (dd, J = 7.8, 1.5 Hz, 1H), 7.62 (m, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.39 (d, J = 8.2 Hz, 1H), 7.32 (d, J = 2.1 Hz, 1H), 7.26 (dd, J = 8.2, 2.1 Hz, 1H), 7.16 (t, J = 7.8 Hz, 1H), 7.09 (dd, J = 7.8, 1.5 Hz, 1H), 6.89 (m, 1H), 2.32 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.26 (s, 1H), 12.57 (s, 1H), 10.91 (s, 1H), 7.69 (d, J=8.3 Hz, 1H), 7.66 (s, 1H), 7.51 (d, J=9.4 Hz, 1H), 7.39 (d, J=8.3 Hz, 1H), 7.32 (d, J=1.9 Hz, 1H), 7.27 (s, 1H), 7.25 (d, J= 1.9 Hz, 1H), 7.17 (d, J=1.9 Hz, 1H), 6.80 (s, 1H), 2.33 (s, 3H), 2.31 (s, 3H)。 Example 48: 5- (4- {N '-[1- (3,4-dimethyl-phenyl) -4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3- Iridene] -hydrazino} -3-hydroxy-benzylidene) -thiazolidine-2,4-dione (Compound 148)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.26 (s, 1H), 12.57 (s, 1H), 10.91 (s, 1H), 7.69 (d, J = 8.3 Hz, 1H), 7.66 (s, 1H), 7.51 (d, J = 9.4 Hz, 1H), 7.39 (d, J = 8.3 Hz, 1H), 7.32 (d, J = 1.9 Hz, 1H), 7.27 (s, 1H), 7.25 (d, J = 1.9 Hz, 1H), 7.17 (d, J = 1.9 Hz, 1H), 6.80 (s, 1H), 2.33 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.33 (s, 1H), 12.58 (s, 1H), 10.94 (s, 1H), 7.76 (d, J=8.3 Hz, 1H), 7.70 (s, 1H), 7.63 (s, 1H), 7.39 (d, J=8.0 Hz, 1H), 7.32 (d, J=1.9 Hz, 1H), 7.27 (dt, J=8.3, 1.9 Hz, 1H), 7.26 (d, J=8.0, 1H), 7.17 (d, J=1.9 Hz, 1H), 6.88 (s, 1H), 2.33 (s, 3H), 2.31 (s, 3H)。 Example 49: 5- (4- {N '-[4-Chloro-1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3- Iridene] -hydrazino} -3-hydroxy-benzylidene) -thiazolidine-2,4-dione (Compound 149)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.33 (s, 1H), 12.58 (s, 1H), 10.94 (s, 1H), 7.76 (d, J = 8.3 Hz, 1H), 7.70 (s, 1H), 7.63 (s, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.32 (d, J = 1.9 Hz, 1H), 7.27 (dt, J = 8.3, 1.9 Hz, 1H), 7.26 ( d, J = 8.0, 1H), 7.17 (d, J = 1.9 Hz, 1H), 6.88 (s, 1H), 2.33 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.12 (s, 1H), 12.33 (s, 1H), 10.68 (s, 1H), 7.92 (d, J=7.8 Hz, 1H), 7.73 (d, J=8.3 Hz, 1H), 7.53-7.52 (m, 2H), 7.39 (d, J=8.4 Hz, 1H), 7.33-7.31 (m, 2H), 7.26 (dd, J=8.3, 2.1 Hz, 1H), 7.15 (d, J=1.8 Hz, 1H), 6.95 (s, 1H), 6.33 (d, J=15.9 Hz, 1H), 2.33 (s, 3H), 2.31 (s, 3H)。 Example 50: 3- (4- {N '-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino } -3-Hydroxy-phenyl) -acrylic acid (Compound 150)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.12 (s, 1H), 12.33 (s, 1H), 10.68 (s, 1H), 7.92 (d, J = 7.8 Hz, 1H), 7.73 (d, J = 8.3 Hz, 1H), 7.53-7.52 (m, 2H), 7.39 (d, J = 8.4 Hz, 1H), 7.33-7.31 (m, 2H), 7.26 (dd, J = 8.3, 2.1 Hz, 1H ), 7.15 (d, J = 1.8 Hz, 1H), 6.95 (s, 1H), 6.33 (d, J = 15.9 Hz, 1H), 2.33 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.81 (s, 1H), 13.14 (s, 1H), 10.90 (s, 1H), 7.92 (d, J=7.8 Hz, 1H), 7.82 (d, J=8.3 Hz, 1H), 7.56-7.55 (m, 2H), 7.39 (d, J=8.0 Hz, 1H), 7.33 (d, J=2.1 Hz, 1H), 7.29-7.27 (m, 2H), 7.15 (d, J=1.8 Hz, 1H), 6.96 (m, 1H), 2.33 (s, 3H), 2.31 (s, 3H)。 Example 51: 1- (3,4-dimethyl-phenyl) -3-{[2-hydroxy-4- (4-oxo-2-thioxo-thiazolidine-5-ylidenemethyl) -phenyl] -hydrazono} -6- Trifluoromethyl-1,3-dihydro-indol-2-one (Compound 151)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.81 (s, 1H), 13.14 (s, 1H), 10.90 (s, 1H), 7.92 (d, J = 7.8 Hz, 1H), 7.82 (d, J = 8.3 Hz, 1H), 7.56-7.55 (m, 2H), 7.39 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 2.1 Hz, 1H), 7.29-7.27 (m, 2H), 7.15 (d, J = 1.8 Hz, 1H), 6.96 (m, 1H), 2.33 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.81 (s, 1H), 13.27 (s, 1H), 10.94 (s, 1H), 7.70 (d, J=8.4 Hz, 1H), 7.55 (s, 1H), 7.52 (d, J=9.9 Hz, 1H), 7.39 (d, J=8.0 Hz, 1H), 7.32-7.30 (m, 2H), 7.26 (dd, J=8.0, 1.6 Hz, 1H), 7.16 (s, 1H), 6.81 (s, 1H), 2.33 (s, 3H), 2.31 (s, 3H)。 Example 52: 1- (3,4-Dimethyl-phenyl) -4-fluoro-3-{[2-hydroxy-4- (4-oxo-2-thioxo-thiazolidine-5-ylidenemethyl) -phenyl] -hydrazono } -6-Trifluoromethyl-1,3-dihydro-indol-2-one (Compound 152)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.81 (s, 1H), 13.27 (s, 1H), 10.94 (s, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.55 (s, 1H), 7.52 (d, J = 9.9 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.32-7.30 (m, 2H), 7.26 (dd, J = 8.0, 1.6 Hz, 1H), 7.16 (s, 1H), 6.81 (s, 1H), 2.33 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.16 (s, 1H), 8.05 (s, 1H), 7.91 (d, J=7.7 Hz, 1H), 7.81 (m, 1H), 7.53 (d, J=7.7, 1H), 7.39 (d, J=8.2 Hz, 1H), 7.33 (d, J=2.0 Hz, 1H), 7.27 (dd, J=8.2, 2.0 Hz, 1H), 7.17-7.12 (m, 2H), 6.95 (s, 1H), 2.33 (s, 3H), 2.31 (s, 3H)。 Example 53: 5- (3- {N '-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino } -2-Hydroxy-benzylidene) -thiazolidine-2,4-dione (Compound 153)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.16 (s, 1H), 8.05 (s, 1H), 7.91 (d, J = 7.7 Hz, 1H), 7.81 (m, 1H), 7.53 (d, J = 7.7, 1H), 7.39 (d, J = 8.2 Hz, 1H), 7.33 (d, J = 2.0 Hz, 1H), 7.27 (dd, J = 8.2, 2.0 Hz, 1H), 7.17-7.12 (m , 2H), 6.95 (s, 1H), 2.33 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.09 (s, 1H), 13.02 (s, 1H), 9.35 (s, 1H), 8.12 (t, J=1.6 Hz, 1H), 7.94 (ddd, J=7.8, 1.6, 1.2 Hz, 1H), 7.81-7.78 (m, 2H), 7.76 (d, J=2.2 Hz, 1H), 7.60 (t, J=7.8 Hz, 1H), 7.43 (d, J=8.8 Hz, 2H), 7.41 (d, J=8.8 Hz, 2H), 7.30 (dd, J=8.4, 2.2 Hz, 1H), 7.12 (t, J=7.8 Hz, 1H), 7.03 (dd, J=7.8, 1.6 Hz, 1H), 6.87 (d, J=8.4 Hz, 1H), 2.65 (t, J=7.4 Hz, 2H), 1.66 (sext, J=7.4 Hz, 2H), 0.94 (t, J=7.4 Hz, 3H)。 Example 54: 3 ′-{N ′-[5-chloro-2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy -Biphenyl-3-carboxylic acid (Compound 154)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.09 (s, 1H), 13.02 (s, 1H), 9.35 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.8, 1.6, 1.2 Hz, 1H), 7.81-7.78 (m, 2H), 7.76 (d, J = 2.2 Hz, 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.43 (d, J = 8.8 Hz, 2H), 7.41 (d, J = 8.8 Hz, 2H), 7.30 (dd, J = 8.4, 2.2 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 7.03 (dd, J = 7.8, 1.6 Hz, 1H), 6.87 (d, J = 8.4 Hz, 1H), 2.65 (t, J = 7.4 Hz, 2H), 1.66 (sext, J = 7.4 Hz, 2H), 0.94 (t, J = 7.4 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.05 (s, 1H), 13.03 (s, 1H), 9.28 (s, 1H), 8.12 (t, J=1.7 Hz, 1H), 7.94 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.79 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.74-7.72 (m, 2H), 7.60 (t, J=7.7 Hz, 1H), 7.49 (d, J=9.0 Hz, 2H), 7.46 (d, J=9.0 Hz, 2H), 7.29 (td, J=7.7, 1.2 Hz, 1H), 7.20 (td, J=7.7, 0.8 Hz, 1H), 7.11 (t, J=7.8 Hz, 1H), 7.00 (dd, J=7.8, 1.6 Hz, 1H), 6.88 (dd, J=7.7, 0.8 Hz, 1H), 2.55 (s, 3H)。 Example 55: 2′-hydroxy-3 ′-{N ′-[1- (4-methylsulfanyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl- 3-carboxylic acid (compound 155)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.05 (s, 1H), 13.03 (s, 1H), 9.28 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 7.94 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.74-7.72 (m, 2H), 7.60 (t, J = 7.7 Hz, 1H), 7.49 (d, J = 9.0 Hz, 2H), 7.46 (d, J = 9.0 Hz, 2H), 7.29 (td, J = 7.7, 1.2 Hz, 1H), 7.20 (td, J = 7.7, 0.8 Hz, 1H) , 7.11 (t, J = 7.8 Hz, 1H), 7.00 (dd, J = 7.8, 1.6 Hz, 1H), 6.88 (dd, J = 7.7, 0.8 Hz, 1H), 2.55 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.07 (s, 1H), 13.03 (s, 1H), 9.28 (s, 1H), 8.12 (t, J=1.7 Hz, 1H), 7.94 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.79 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.74 (m, 1H), 7.73 (dd, J=7.9, 1.6 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.54 (d, J=9.0 Hz, 2H), 7.52 (d, J=9.0 Hz, 2H), 7.29 (td, J=7.8, 1.2 Hz, 1H), 7.20 (td, J=7.8, 0.8 Hz, 1H), 7.12 (t, J=7.9 Hz, 1H), 7.01 (dd, J=7.9, 1.6 Hz, 1H), 6.90 (dd, J=7.8, 0.8 Hz, 1H), 4.52 (s, 2H), 3.36 (s, 3H)。 Example 56: 2′-hydroxy-3 ′-{N ′-[1- (4-methoxymethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl- 3-carboxylic acid (compound 156)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.07 (s, 1H), 13.03 (s, 1H), 9.28 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 7.94 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.74 (m, 1H), 7.73 (dd, J = 7.9, 1.6 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.54 (d, J = 9.0 Hz, 2H), 7.52 (d, J = 9.0 Hz, 2H), 7.29 (td, J = 7.8, 1.2 Hz, 1H), 7.20 (td, J = 7.8, 0.8 Hz, 1H), 7.12 (t, J = 7.9 Hz, 1H), 7.01 (dd, J = 7.9, 1.6 Hz, 1H), 6.90 (dd, J = 7.8, 0.8 Hz, 1H), 4.52 (s, 2H), 3.36 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.06 (s, 1H), 13.03 (s, 1H), 9.29 (s, 1H), 8.12 (s, 1H), 7.94 (d, J=7.6 Hz, 1H), 7.83-7.72 (m, 5H), 7.62-7.58 (m, 3H), 7.30 (t, J=7.9 Hz, 1H), 7.21 (t, J=7.9 Hz, 1H), 7.12 (t, J=7.8 Hz, 1H), 7.01 (d, J=7.8 Hz, 1H), 6.93 (d, J=7.9 Hz, 1H), 6.77 (s, 1H), 1.76 (s, 3H)。 Example 57: (±) -2′-hydroxy-3 ′-(N ′-{2-oxo-1- [4- (2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl)) -Phenyl] -1,2-dihydro-indole-3-ylidene} -hydrazino) -biphenyl-3-carboxylic acid (Compound 157)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.06 (s, 1H), 13.03 (s, 1H), 9.29 (s, 1H), 8.12 (s, 1H), 7.94 (d, J = 7.6 Hz, 1H), 7.83-7.72 (m, 5H), 7.62-7.58 (m, 3H), 7.30 (t, J = 7.9 Hz, 1H), 7.21 (t, J = 7.9 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 7.01 (d, J = 7.8 Hz, 1H), 6.93 (d, J = 7.9 Hz, 1H), 6.77 (s, 1H), 1.76 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.07 (s, 1H), 13.03 (s, 1H), 9.37 (s, 1H), 8.12 (s, 1H), 7.94 (d, J=7.6 Hz, 1H), 7.88 (s, 1H), 7.81-7.75 (m, 3H), 7.68 (d, J=8.1 Hz, 1H), 7.63-7.57 (m, 2H), 7.15-7.09 (m, 2H), 7.04 (d, J=7.6 Hz, 1H), 6.93 (m, 1H), 2.54 (s, 3H)。 Example 58: 3 ′-{N ′-[5-fluoro-1- (4-methyl-3-trifluoromethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino } -2'-Hydroxy-biphenyl-3-carboxylic acid (Compound 158)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.07 (s, 1H), 13.03 (s, 1H), 9.37 (s, 1H), 8.12 (s, 1H), 7.94 (d, J = 7.6 Hz, 1H), 7.88 (s, 1H), 7.81-7.75 (m, 3H), 7.68 (d, J = 8.1 Hz, 1H), 7.63-7.57 (m, 2H), 7.15-7.09 (m, 2H), 7.04 (d, J = 7.6 Hz, 1H), 6.93 (m, 1H), 2.54 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.05 (s, 1H), 13.02 (s, 1H), 9.29 (s, 1H), 8.12 (s, 1H), 7.94 (d, J=7.8 Hz, 1H), 7.81-7.72 (m, 5H), 7.68-7.65 (m, 2H), 7.60 (t, J=7.8 Hz, 1H), 7.31 (t, J=7.6 Hz, 1H), 7.22 (t, J=7.6 Hz, 1H), 7.12 (t, J=7.9 Hz, 1H), 7.03 (d, J=7.8 Hz, 1H), 6.99 (d, J=7.8 Hz, 1H), 3.24 (s, 3H), 1.85 (s, 3H)。 Example 59: 2'-hydroxy-3 '-(N'-{2-oxo-1- [4- (2,2,2-trifluoro-1-methoxy-1-methyl-ethyl) -phenyl]- 1,2-Dihydro-indole-3-ylidene} -hydrazino) -biphenyl-3-carboxylic acid (Compound 159)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.05 (s, 1H), 13.02 (s, 1H), 9.29 (s, 1H), 8.12 (s, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.81-7.72 (m, 5H), 7.68-7.65 (m, 2H), 7.60 (t, J = 7.8 Hz, 1H), 7.31 (t, J = 7.6 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H), 7.12 (t, J = 7.9 Hz, 1H), 7.03 (d, J = 7.8 Hz, 1H), 6.99 (d, J = 7.8 Hz, 1H), 3.24 (s, 3H), 1.85 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.03 (s, 1H), 12.99 (s, 1H), 9.27 (s, 1H), 8.12 (t, J=1.5 Hz, 1H), 7.94 (ddd, J=7.7, 1.5, 1.2 Hz, 1H), 7.79 (ddd, J=7.7, 1.5, 1.2 Hz, 1H), 7.74 (dd, J=8.4, 5.3 Hz, 1H), 7.72 (dd, J=7.8, 1.4 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.36 (d, J=8.0 Hz, 1H), 7.31 (d, J=1.8 Hz, 1H), 7.25 (dd, J=7.8, 1.8 Hz, 1H), 7.11 (t, J=7.8 Hz, 1H), 7.03-6.98 (m, 2H), 6.66 (dd, J=9.3, 2.2 Hz, 1H), 2.31 (s, 3H), 2.30 (s, 3H)。 Example 60: 3 '-{N'-[1- (3,4-dimethyl-phenyl) -6-fluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid (Compound 160)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.03 (s, 1H), 12.99 (s, 1H), 9.27 (s, 1H), 8.12 (t, J = 1.5 Hz, 1H), 7.94 (ddd, J = 7.7, 1.5, 1.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.5, 1.2 Hz, 1H), 7.74 (dd, J = 8.4, 5.3 Hz, 1H), 7.72 (dd, J = 7.8, 1.4 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.31 (d, J = 1.8 Hz, 1H), 7.25 (dd, J = 7.8, 1.8 Hz, 1H), 7.11 (t, J = 7.8 Hz, 1H), 7.03-6.98 (m, 2H), 6.66 (dd, J = 9.3, 2.2 Hz, 1H), 2.31 (s, 3H), 2.30 ( s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.02 (s, 1H), 12.98 (s, 1H), 9.28 (s, 1H), 8.11 (t, J=1.6 Hz, 1H), 7.94 (ddd, J=7.8, 1.6, 1.1 Hz, 1H), 7.79 (m, 1H), 7.75 (dd, J=7.7, 4.9 Hz, 1H), 7.73 (dd, J=7.8, 1.5 Hz, 1H), 7.59 (t, J=7.8 Hz, 1H), 7.48 (d, J=9.2 Hz, 2H), 7.46 (d, J=9.2 Hz, 2H), 7.11 (t, J=7.8 Hz, 1H), 7.02 (m, 1H), 7.00 (dd, J=7.8, 1.5 Hz, 1H), 6.69 (dd, J=9.3, 2.2 Hz, 1H), 3.01 (sept, J=6.9 Hz, 1H), 1.27 (d, J=6.9 Hz, 6H)。 Example 61: 3 ′-{N ′-[6-fluoro-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy -Biphenyl-3-carboxylic acid (Compound 161)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.02 (s, 1H), 12.98 (s, 1H), 9.28 (s, 1H), 8.11 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.8, 1.6, 1.1 Hz, 1H), 7.79 (m, 1H), 7.75 (dd, J = 7.7, 4.9 Hz, 1H), 7.73 (dd, J = 7.8, 1.5 Hz, 1H), 7.59 (t , J = 7.8 Hz, 1H), 7.48 (d, J = 9.2 Hz, 2H), 7.46 (d, J = 9.2 Hz, 2H), 7.11 (t, J = 7.8 Hz, 1H), 7.02 (m, 1H ), 7.00 (dd, J = 7.8, 1.5 Hz, 1H), 6.69 (dd, J = 9.3, 2.2 Hz, 1H), 3.01 (sept, J = 6.9 Hz, 1H), 1.27 (d, J = 6.9 Hz , 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.12 (s, 1H), 12.99 (s, 1H), 9.38 (s, 1H), 8.12 (t, J=1.6 Hz, 1H), 8.03 (m, 1H), 7.94 (ddd, J=7.8, 1.6, 1.1 Hz, 1H), 7.85 (dd, J=7.8, 1.5 Hz, 1H), 7.80 (ddd, J=7.8, 1.6, 1.1 Hz, 1H), 7.62 (m, 1H), 7.60 (t, J=7.8 Hz, 1H), 7.37 (d, J=8.0 Hz, 1H), 7.33 (d, J=1.9 Hz, 1H), 7.26 (dd, J=8.0, 1.9 Hz, 1H), 7.13 (t, J=7.8 Hz, 1H), 7.05 (dd, J=7.8, 1.5 Hz, 1H), 7.01 (d, J=8.3 Hz, 1H), 2.32 (s, 3H), 2.31 (s, 3H)。 Example 62: 3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-5-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 162)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.12 (s, 1H), 12.99 (s, 1H), 9.38 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 8.03 (m, 1H), 7.94 (ddd, J = 7.8, 1.6, 1.1 Hz, 1H), 7.85 (dd, J = 7.8, 1.5 Hz, 1H), 7.80 (ddd, J = 7.8, 1.6, 1.1 Hz, 1H), 7.62 (m, 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 1.9 Hz, 1H), 7.26 (dd, J = 8.0, 1.9 Hz, 1H), 7.13 (t, J = 7.8 Hz, 1H), 7.05 (dd, J = 7.8, 1.5 Hz, 1H), 7.01 (d, J = 8.3 Hz, 1H), 2.32 (s, 3H) , 2.31 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 12.98 (s, 1H), 9.28 (s, 1H), 8.11 (t, J=1.7 Hz, 1H), 7.94 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.79 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.75 (dd, J=7.5, 4.7 Hz, 1H), 7.72 (dd, J=7.8, 1.6 Hz, 1H), 7.59 (t, J=7.7 Hz, 1H), 7.45 (d, J=8.5 Hz, 2H), 7.42 (d, J=8.5 Hz, 2H), 7.11 (t, J=7.8 Hz, 1H), 7.02 (m, 1H), 7.00 (dd, J=7.8, 1.6 Hz, 1H), 6.68 (dd, J=9.4, 2.3 Hz, 1H), 2.66 (t, J=7.4 Hz, 2H), 1.66 (sext, J=7.4 Hz, 2H), 0.95 (t, J=7.4 Hz, 3H)。 Example 63: 3 ′-{N ′-[6-fluoro-2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy -Biphenyl-3-carboxylic acid (Compound 163)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 12.98 (s, 1H), 9.28 (s, 1H), 8.11 (t, J = 1.7 Hz, 1H), 7.94 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.75 (dd, J = 7.5, 4.7 Hz, 1H), 7.72 (dd, J = 7.8, 1.6 Hz, 1H), 7.59 (t, J = 7.7 Hz, 1H), 7.45 (d, J = 8.5 Hz, 2H), 7.42 (d, J = 8.5 Hz, 2H), 7.11 (t, J = 7.8 Hz, 1H), 7.02 (m , 1H), 7.00 (dd, J = 7.8, 1.6 Hz, 1H), 6.68 (dd, J = 9.4, 2.3 Hz, 1H), 2.66 (t, J = 7.4 Hz, 2H), 1.66 (sext, J = 7.4 Hz, 2H), 0.95 (t, J = 7.4 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.11 (s, 1H), 12.99 (s, 1H), 9.38 (s, 1H), 8.12 (t, J=1.7 Hz, 1H), 8.03 (d, J=1.5 Hz, 1H), 7.95 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.85 (dd, J=8.2, 1.5 Hz, 1H), 7.80 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.62 (m, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.46 (d, J=8.6 Hz, 2H), 7.43 (d, J=8.6 Hz, 2H), 7.13 (t, J=7.8 Hz, 1H), 7.05 (dd, J=7.8, 1.6 Hz, 1H), 7.02 (d, J=8.2 Hz, 1H), 2.66 (t, J=7.4 Hz, 2H), 1.67 (sext, J=7.4 Hz, 2H), 0.95 (t, J=7.4 Hz, 3H)。 Example 64: 2'-hydroxy-3 '-{N'-[2-oxo-1- (4-propyl-phenyl) -5-trifluoromethyl-1,2-dihydro-indole-3-ylidene]- Hydrazino} -biphenyl-3-carboxylic acid (compound 164)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.11 (s, 1H), 12.99 (s, 1H), 9.38 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 8.03 (d, J = 1.5 Hz, 1H), 7.95 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.85 (dd, J = 8.2, 1.5 Hz, 1H), 7.80 (ddd, J = 7.7, 1.7, 1.2 Hz , 1H), 7.62 (m, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.46 (d, J = 8.6 Hz, 2H), 7.43 (d, J = 8.6 Hz, 2H), 7.13 (t , J = 7.8 Hz, 1H), 7.05 (dd, J = 7.8, 1.6 Hz, 1H), 7.02 (d, J = 8.2 Hz, 1H), 2.66 (t, J = 7.4 Hz, 2H), 1.67 (sext , J = 7.4 Hz, 2H), 0.95 (t, J = 7.4 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.25 (s, 1H), 13.01 (s, 1H), 9.39 (s, 1H), 8.12 (t, J=1.6 Hz, 1H), 7.94 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.79 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.64 (dd, J=7.8, 1.6 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.47 (d, J=8.7 Hz, 2H), 7.43 (d, J=8.7 Hz, 2H), 7.29 (dt, J=11.2, 8.5 Hz, 1H), 7.14 (t, J=7.8 Hz, 1H), 7.05 (dd, J=7.8, 1.6 Hz, 1H), 6.65 (dd, J=8.5, 3.1 Hz, 1H), 3.00 (sept, J=7.0 Hz, 1H), 1.27 (d, J=7.0 Hz, 6H)。 Example 65: 3 '-{N'-[4,5-difluoro-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid (Compound 165)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.25 (s, 1H), 13.01 (s, 1H), 9.39 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.64 (dd, J = 7.8, 1.6 Hz, 1H), 7.60 (t, J = 7.7 Hz , 1H), 7.47 (d, J = 8.7 Hz, 2H), 7.43 (d, J = 8.7 Hz, 2H), 7.29 (dt, J = 11.2, 8.5 Hz, 1H), 7.14 (t, J = 7.8 Hz , 1H), 7.05 (dd, J = 7.8, 1.6 Hz, 1H), 6.65 (dd, J = 8.5, 3.1 Hz, 1H), 3.00 (sept, J = 7.0 Hz, 1H), 1.27 (d, J = 7.0 Hz, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.15 (s, 1H), 8.13 (t, J=1.4 Hz, 1H), 7.91 (d, J=7.8 Hz, 1H), 7.68 (d, J=7.8 Hz, 1H), 7.66-7.63 (m, 2H), 7.51 (t, J=7.8 Hz, 1H), 7.38 (d, J=7.6 Hz, 1H), 7.28 (td, J=7.6, 1.0 Hz, 1H), 7.11 (t, J=7.6 Hz, 1H), 7.03 (t, J=7.6 Hz, 1H), 6.96 (dd, J=7.6, 1.5 Hz, 1H), 4.42 (m, 1H), 3.26 (m, 2H), 2.84 (m, 2H), 2.45 (m, 2H), 1.76 (m, 2H)。 Example 66: 2′-Hydroxy-3 ′-[N ′-(2-oxo-1-piperidin-4-yl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid Acid (Compound 166)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.15 (s, 1H), 8.13 (t, J = 1.4 Hz, 1H), 7.91 (d, J = 7.8 Hz, 1H), 7.68 (d, J = 7.8 Hz, 1H), 7.66-7.63 (m, 2H), 7.51 (t, J = 7.8 Hz, 1H), 7.38 (d, J = 7.6 Hz, 1H), 7.28 (td, J = 7.6, 1.0 Hz, 1H), 7.11 (t, J = 7.6 Hz, 1H), 7.03 (t, J = 7.6 Hz, 1H), 6.96 (dd, J = 7.6, 1.5 Hz, 1H), 4.42 (m, 1H), 3.26 ( m, 2H), 2.84 (m, 2H), 2.45 (m, 2H), 1.76 (m, 2H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.05 (s, 1H), 13.02 (s, 1H), 9.37 (s, 1H), 8.12 (t, J=1.7 Hz, 1H), 7.94 (ddd, J=7.8, 1.7, 1.3 Hz, 1H), 7.79 (m, 1H), 7.78 (dd, J=7.8, 1.5 Hz, 1H), 7.60 (t, J=7.8 Hz, 1H), 7.58 (dd, J=8.2, 2.7 Hz, 1H), 7.52 (t, J=8.1 Hz, 1H), 7.37 (dd, J=11.3, 1.2 Hz, 1H), 7.25 (dd, J=8.1, 1.2 Hz, 1H), 7.13 (t, J=7.8 Hz, 1H), 7.11 (ddd, J=9.2, 8.7, 2.7 Hz, 1H), 7.04 (dd, J=7.8, 1.5 Hz, 1H, 6.72 (ddd, J=8.7, 4.1, 1.0 Hz, 1H), 2.43 (s, 3H)。 Example 67: 3 '-{N'-[5-fluoro-1- (2-fluoro-4-methyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 167)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.05 (s, 1H), 13.02 (s, 1H), 9.37 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 7.94 (ddd, J = 7.8, 1.7, 1.3 Hz, 1H), 7.79 (m, 1H), 7.78 (dd, J = 7.8, 1.5 Hz, 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.58 (dd, J = 8.2, 2.7 Hz, 1H), 7.52 (t, J = 8.1 Hz, 1H), 7.37 (dd, J = 11.3, 1.2 Hz, 1H), 7.25 (dd, J = 8.1, 1.2 Hz, 1H), 7.13 (t, J = 7.8 Hz, 1H), 7.11 (ddd, J = 9.2, 8.7, 2.7 Hz, 1H), 7.04 (dd, J = 7.8, 1.5 Hz, 1H, 6.72 (ddd, J = 8.7, 4.1, 1.0 Hz, 1H), 2.43 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.05 (s, 1H), 13.03 (s, 1H), 9.24 (s, 1H), 8.12 (t, J=1.7 Hz, 1H), 7.94 (ddd, J=7.7, 1.7, 1.1 Hz, 1H), 7.79 (ddd, J=7.7, 1.7, 1.1 Hz, 1H), 7.68 (dd, J=7.9, 1.6 Hz, 1H), 7.63 (dd, J=7.7, 1.0 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.35 (td, J=7.7, 1.0 Hz, 1H), 7.16-7.12 (m, 2H), 7.09 (t, J=7.9 Hz, 1H), 6.98 (dd, J=7.9, 1.6 Hz, 1H), 3.28 (s, 3H)。 Example 68: 2′-hydroxy-3 ′-[N ′-(1-methyl-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid (Compound 168) )

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.05 (s, 1H), 13.03 (s, 1H), 9.24 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 7.94 (ddd, J = 7.7, 1.7, 1.1 Hz, 1H), 7.79 (ddd, J = 7.7, 1.7, 1.1 Hz, 1H), 7.68 (dd, J = 7.9, 1.6 Hz, 1H), 7.63 (dd, J = 7.7, 1.0 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.35 (td, J = 7.7, 1.0 Hz, 1H), 7.16-7.12 (m, 2H), 7.09 (t, J = 7.9 Hz, 1H), 6.98 (dd, J = 7.9, 1.6 Hz, 1H), 3.28 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.12 (s, 1H), 13.00 (s, 1H), 9.23 (s, 1H), 8.13 (t, J=1.7 Hz, 1H), 7.94 (ddd, J=7.8, 1.7, 1.1 Hz, 1H), 7.79 (ddd, J=7.6, 1.7, 1.1 Hz, 1H), 7.68 (dd, J=7.8, 1.6 Hz, 1H), 7.65 (dd, J=7.6, 1.1 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.32 (td, J=7.6, 1.1 Hz, 1H), 7.21 (dd, J=7.6, 0.8 Hz, 1H), 7.13 (td, J=7.6, 0.8 Hz, 1H), 7.09 (t, J=7.8 Hz, 1H), 6.98 (dd, J=7.8, 1.6 Hz, 1H), 4.76 (qn, J=8.5 Hz, 1H), 2.10 (m, 2H), 1.97-1.89 (m, 4H), 1.68 (m, 2H)。 Example 69: 3 ′-[N ′-(1-cyclopentyl-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2′-hydroxy-biphenyl-3-carboxylic acid (Compound 169 )

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.12 (s, 1H), 13.00 (s, 1H), 9.23 (s, 1H), 8.13 (t, J = 1.7 Hz, 1H), 7.94 (ddd, J = 7.8, 1.7, 1.1 Hz, 1H), 7.79 (ddd, J = 7.6, 1.7, 1.1 Hz, 1H), 7.68 (dd, J = 7.8, 1.6 Hz, 1H), 7.65 (dd, J = 7.6, 1.1 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.32 (td, J = 7.6, 1.1 Hz, 1H), 7.21 (dd, J = 7.6, 0.8 Hz, 1H), 7.13 (td, J = 7.6, 0.8 Hz, 1H), 7.09 (t, J = 7.8 Hz, 1H), 6.98 (dd, J = 7.8, 1.6 Hz, 1H), 4.76 (qn, J = 8.5 Hz, 1H), 2.10 ( m, 2H), 1.97-1.89 (m, 4H), 1.68 (m, 2H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300 MHz, DMSO-d₆) δ 12.98 (s, 2H), 9.22 (s, 1H), 8.12 (t, J=1.6 Hz, 1H), 7.94 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.79 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.70 (dd, J=8.0, 1.5 Hz, 1H), 7.60 (dd, J=7.7, 1.6 Hz, 1H), 7.59 (t, J=7.7 Hz, 1H), 7.35 (d, J=8.0 Hz, 1H), 7.28 (d, J=1.9 Hz, 1H), 7.21 (dd, J=8.0, 1.9 Hz, 1H), 7.10 (t, J=7.7 Hz, 1H), 7.00 (m, 1H), 6.98 (dd, J=7.7, 1.6 Hz, 1H), 6.65 (m, 1H), 2.31 (s, 6H), 2.30 (s, 3H)。 Example 70: 3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -6-methyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ′ -Hydroxy-biphenyl-3-carboxylic acid (Compound 170)

This compound was prepared as described in Scheme II. ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 12.98 (s, 2H), 9.22 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.70 (dd, J = 8.0, 1.5 Hz, 1H), 7.60 (dd, J = 7.7, 1.6 Hz, 1H), 7.59 (t, J = 7.7 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 7.28 (d, J = 1.9 Hz, 1H), 7.21 (dd, J = 8.0, 1.9 Hz, 1H), 7.10 (t, J = 7.7 Hz, 1H), 7.00 (m, 1H), 6.98 (dd, J = 7.7, 1.6 Hz, 1H), 6.65 (m, 1H), 2.31 (s, 6H), 2.30 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.07 (s, 1H), 13.04 (s, 1H), 9.28 (s, 1H), 8.12 (t, J=1.5 Hz, 1H), 7.94 (ddd, J=7.6, 1.5, 1.1 Hz, 1H), 7.79 (ddd, J=7.6, 1.5, 1.1 Hz, 1H), 7.76-7.72 (m, 2H), 7.61 (td, J=7.4, 1.0 Hz, 2H), 7.60 (t, J=7.6 Hz, 1H), 7.55 (dd, J=7.4, 1.0 Hz, 2H), 7.50 (tt, J=7.4, 1.0 Hz, 1H), 7.30 (td, J=7.6, 1.1 Hz, 1H), 7.20 (td, J=7.6, 0.6 Hz, 1H), 7.12 (t, J=7.8 Hz, 1H), 7.01 (dd, J=7.8, 1.5 Hz, 1H), 6.89 (d, J=7.6 Hz, 1H)。 Example 71 2′-hydroxy-3 ′-[N ′-(2-oxo-1-phenyl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid (Compound 171 )

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.07 (s, 1H), 13.04 (s, 1H), 9.28 (s, 1H), 8.12 (t, J = 1.5 Hz, 1H), 7.94 (ddd, J = 7.6, 1.5, 1.1 Hz, 1H), 7.79 (ddd, J = 7.6, 1.5, 1.1 Hz, 1H), 7.76-7.72 (m, 2H), 7.61 (td, J = 7.4, 1.0 Hz, 2H) , 7.60 (t, J = 7.6 Hz, 1H), 7.55 (dd, J = 7.4, 1.0 Hz, 2H), 7.50 (tt, J = 7.4, 1.0 Hz, 1H), 7.30 (td, J = 7.6, 1.1 Hz, 1H), 7.20 (td, J = 7.6, 0.6 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 7.01 (dd, J = 7.8, 1.5 Hz, 1H), 6.89 (d, J = 7.6 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.04 (s, 1H), 12.98 (s, 1H), 9.30 (s, 1H), 8.12 (t, J=1.5 Hz, 1H), 7.94 (ddd, J=7.7, 1.5, 0.9 Hz, 1H), 7.79 (ddd, J=7.7, 1.5, 0.9 Hz, 1H), 7.76 (dd, J=8.5, 5.7 Hz, 1H), 7.73 (dd, J=7.8, 1.2 Hz, 1H), 7.64-7.55 (m, 5H), 7.51 (t, J=7.3 Hz, 1H), 7.11 (t, J=7.8 Hz, 1H), 7.05-6.99 (m, 2H), 6.71 (dd, J=9.4, 2.2 Hz, 1H)。 Example 72: 3 '-[N'-(6-Fluoro-2-oxo-1-phenyl-2,3-dihydro-1H-indol-3-yl) -hydrazino] -2'-hydroxy-biphenyl-3 -Carboxylic acid (Compound 172)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.04 (s, 1H), 12.98 (s, 1H), 9.30 (s, 1H), 8.12 (t, J = 1.5 Hz, 1H), 7.94 (ddd, J = 7.7, 1.5, 0.9 Hz, 1H), 7.79 (ddd, J = 7.7, 1.5, 0.9 Hz, 1H), 7.76 (dd, J = 8.5, 5.7 Hz, 1H), 7.73 (dd, J = 7.8, 1.2 Hz, 1H), 7.64-7.55 (m, 5H), 7.51 (t, J = 7.3 Hz, 1H), 7.11 (t, J = 7.8 Hz, 1H), 7.05-6.99 (m, 2H), 6.71 ( dd, J = 9.4, 2.2 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300 MHz, DMSO-d₆) δ 13.03 (s, 1H), 13.00 (s, 1H), 9.23 (s, 1H), 8.12 (t, J=1.6 Hz, 1H), 7.94 (ddd, J=7.8, 1.6, 1.2 Hz, 1H), 7.79 (ddd, J=7.8, 1.6, 1.2 Hz, 1H), 7.70 (dd, J=7.8, 1.6 Hz, 1H), 7.64 (d, J=7.9 Hz, 1H), 7.59 (t, J=7.8 Hz, 1H), 7.36 (d, J=8.0 Hz, 1H), 7.29 (d, J=2.0 Hz, 1H), 7.23 (dd, J=8.0, 2.0 Hz, 1H), 7.10 (t, J=7.8 Hz, 1H), 7.08 (dd, J=7.9, 1.2 Hz, 1H), 6.98 (dd, J=7.8, 1.6 Hz, 1H), 6.68 (d, J=1.2 Hz, 1H), 2.89 (sept, J=6.8 Hz, 1H), 2.31 (s, 3H), 2.31 (s, 3H), 1.17 (d, J=6.8 Hz, 6H)。 Example 73: 3 '-{N'-[1- (3,4-dimethyl-phenyl) -6-isopropyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid (Compound 173)

This compound was prepared as described in Scheme II. ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 13.03 (s, 1H), 13.00 (s, 1H), 9.23 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.8, 1.6, 1.2 Hz, 1H), 7.79 (ddd, J = 7.8, 1.6, 1.2 Hz, 1H), 7.70 (dd, J = 7.8, 1.6 Hz, 1H), 7.64 (d, J = 7.9 Hz , 1H), 7.59 (t, J = 7.8 Hz, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 2.0 Hz, 1H), 7.23 (dd, J = 8.0, 2.0 Hz , 1H), 7.10 (t, J = 7.8 Hz, 1H), 7.08 (dd, J = 7.9, 1.2 Hz, 1H), 6.98 (dd, J = 7.8, 1.6 Hz, 1H), 6.68 (d, J = 1.2 Hz, 1H), 2.89 (sept, J = 6.8 Hz, 1H), 2.31 (s, 3H), 2.31 (s, 3H), 1.17 (d, J = 6.8 Hz, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300 MHz, DMSO-d₆) δ 13.29 (s, 1H), 8.13 (s, 1H), 7.94 (d, J=7.6 Hz, 1H), 7.76 (d, J=7.6 Hz, 1H), 7.61-7.54 (m, 2H), 7.35 (d, J=8.3 Hz, 1H), 7.28 (m, 1H), 7.22 (m, 2H), 7.16-7.10 (m, 2H), 6.98 (dd, J=7.6, 1.1 Hz, 1H), 6.65 (d, J=7.6 Hz, 1H), 3.99 (m, 1H), 2.31 (s, 3H), 2.30 (s, 3H), 1.38 (d, J=6.9 Hz, 6H)。 Example 74: 3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -4-isopropyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ′ -Hydroxy-biphenyl-3-carboxylic acid (Compound 174)

This compound was prepared as described in Scheme II. ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 13.29 (s, 1H), 8.13 (s, 1H), 7.94 (d, J = 7.6 Hz, 1H), 7.76 (d, J = 7.6 Hz, 1H) , 7.61-7.54 (m, 2H), 7.35 (d, J = 8.3 Hz, 1H), 7.28 (m, 1H), 7.22 (m, 2H), 7.16-7.10 (m, 2H), 6.98 (dd, J = 7.6, 1.1 Hz, 1H), 6.65 (d, J = 7.6 Hz, 1H), 3.99 (m, 1H), 2.31 (s, 3H), 2.30 (s, 3H), 1.38 (d, J = 6.9 Hz , 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.22 (s, 1H), 9.44 (s, 1H), 8.01 (dd, J=7.0, 2.4 Hz, 1H), 7.92 (d, J=7.8 Hz, 1H), 7.78 (dd, J=7.8, 1.5 Hz, 1H), 7.78 (m, 1H), 7.54 (d, J=7.8 Hz, 1H), 7.41 (dd, J=10.4, 8.4 Hz, 1H), 7.39 (d, J=7.9 Hz, 1H), 7.33 (d, J=1.9 Hz, 1H), 7.27 (dd, J=7.9, 1.9 Hz, 1H), 7.13 (t, J=7.8 Hz, 1H), 7.05 (dd, J=7.8, 1.5 Hz, 1H), 6.96 (s, 1H), 2.32 (s, 3H), 2.31 (s, 3H)。 Example 75: 3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 4-Fluoro-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 175)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.22 (s, 1H), 9.44 (s, 1H), 8.01 (dd, J = 7.0, 2.4 Hz, 1H), 7.92 (d, J = 7.8 Hz, 1H), 7.78 (dd, J = 7.8, 1.5 Hz, 1H), 7.78 (m, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.41 (dd, J = 10.4, 8.4 Hz, 1H), 7.39 (d, J = 7.9 Hz, 1H), 7.33 (d, J = 1.9 Hz, 1H), 7.27 (dd, J = 7.9, 1.9 Hz, 1H), 7.13 (t, J = 7.8 Hz, 1H), 7.05 (dd, J = 7.8, 1.5 Hz, 1H), 6.96 (s, 1H), 2.32 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300 MHz, DMSO-d₆) δ 13.38 (s, 1H), 13.11 (s, 1H), 9.70 (s, 1H), 8.02 (d, J=8.0 Hz, 1 H), 8.02 (dd, J=6.9, 2.4 Hz, 1H), 7.80 (ddd, J=8.5, 4.6, 2.4 Hz, 1H), 7.76 (d, J=2.6 Hz, 1H), 7.54 (d, J=8.0 Hz, 1H), 7.42 (dd, J=10.7, 8.5 Hz, 1H), 7.39 (d, J=7.9 Hz, 1H), 7.33 (d, J=2.0 Hz, 1H), 7.27 (dd, J=7.9, 2.0 Hz, 1H), 7.08 (d, J=2.6 Hz, 1H), 6.95 (s, 1H), 2.32 (s, 3H), 2.31 (s, 3H)。 Example 76: 5′-chloro-3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] -Hydrazino} -4-fluoro-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 176)

This compound was prepared as described in Scheme II. ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 13.38 (s, 1H), 13.11 (s, 1H), 9.70 (s, 1H), 8.02 (d, J = 8.0 Hz, 1 H), 8.02 (dd , J = 6.9, 2.4 Hz, 1H), 7.80 (ddd, J = 8.5, 4.6, 2.4 Hz, 1H), 7.76 (d, J = 2.6 Hz, 1H), 7.54 (d, J = 8.0 Hz, 1H) , 7.42 (dd, J = 10.7, 8.5 Hz, 1H), 7.39 (d, J = 7.9 Hz, 1H), 7.33 (d, J = 2.0 Hz, 1H), 7.27 (dd, J = 7.9, 2.0 Hz, 1H), 7.08 (d, J = 2.6 Hz, 1H), 6.95 (s, 1H), 2.32 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300 MHz, DMSO-d₆) δ 13.19 (s, 1H), 13.13 (s, 1H), 9.56 (s, 1H), 7.98 (m, 1H), 7.92 (d, J=7.8 Hz, 1H), 7.82 (dd, J=7.7, 1.1 Hz, 1H), 7.54 (d, J=7.8 Hz, 1H), 7.44 (m, 1H), 7.38 (d, J=8.0 Hz, 1H), 7.33 (d, J=1.7 Hz, 1H), 7.26 (dd, J=8.0, 1.7 Hz, 1H), 7.11 (t, J=7.7 Hz, 1H), 7.00 (dd, J=7.7, 1.1 Hz, 1H), 6.95 (s, 1H), 2.32 (s, 3H), 2.31 (s, 3H)。 Example 77: 3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 6-Fluoro-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 177)

This compound was prepared as described in Scheme II. ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 13.19 (s, 1H), 13.13 (s, 1H), 9.56 (s, 1H), 7.98 (m, 1H), 7.92 (d, J = 7.8 Hz, 1H), 7.82 (dd, J = 7.7, 1.1 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.44 (m, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.33 ( d, J = 1.7 Hz, 1H), 7.26 (dd, J = 8.0, 1.7 Hz, 1H), 7.11 (t, J = 7.7 Hz, 1H), 7.00 (dd, J = 7.7, 1.1 Hz, 1H), 6.95 (s, 1H), 2.32 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.27 (s, 1H), 13.05 (s, 1H), 9.40 (s, 1H), 8.12 (t, J=1.7 Hz, 1H), 7.94 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.79 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.64 (dd, J=7.9, 1.6 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.36 (d, J=8.2 Hz, 1H), 7.29 (dt, J=11.1, 8.5 Hz, 1H), 7.29 (d, J=2.1 Hz, 1H), 7.22 (dd, J=8.2, 2.1 Hz, 1H), 7.14 (t, J=7.9 Hz, 1H), 7.05 (dd, J=7.9, 1.6 Hz, 1H), 6.63 (dd, J=8.5, 3.2 Hz, 1H), 2.31 (s, 3H), 2.29 (s, 3H)。 Example 78: 3 '-{N'-[1- (3,4-dimethyl-phenyl) -4,5-difluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 178)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.27 (s, 1H), 13.05 (s, 1H), 9.40 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 7.94 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.64 (dd, J = 7.9, 1.6 Hz, 1H), 7.60 (t, J = 7.7 Hz , 1H), 7.36 (d, J = 8.2 Hz, 1H), 7.29 (dt, J = 11.1, 8.5 Hz, 1H), 7.29 (d, J = 2.1 Hz, 1H), 7.22 (dd, J = 8.2, 2.1 Hz, 1H), 7.14 (t, J = 7.9 Hz, 1H), 7.05 (dd, J = 7.9, 1.6 Hz, 1H), 6.63 (dd, J = 8.5, 3.2 Hz, 1H), 2.31 (s, 3H), 2.29 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.23 (s, 1H), 12.83 (s, 1H), 9.43 (s, 1H), 7.92 (d, J=7.9 Hz, 1H), 7.91 (d, J=7.9 Hz, 1H), 7.78 (dd, J=7.8, 1.5 Hz, 1H), 7.54 (d, J=7.9 Hz, 1H), 7.49 (s, 1H), 7.46 (d, J=7.9 Hz, 1H), 7.39 (d, J=7.9 Hz, 1H), 7.33 (d, J=1.8 Hz, 1H), 7.27 (dd, J=7.9, 1.8 Hz, 1H), 7.13 (t, J=7.8 Hz, 1H), 7.05 (dd, J=7.8, 1.6 Hz, 1H), 6.96 (s, 1H), 2.59 (s, 3H), 2.32 (s, 3H), 2.31 (s, 3H)。 Example 79: 3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-3-methyl-biphenyl-4-carboxylic acid (Compound 179)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.23 (s, 1H), 12.83 (s, 1H), 9.43 (s, 1H), 7.92 (d, J = 7.9 Hz, 1H), 7.91 (d, J = 7.9 Hz, 1H), 7.78 (dd, J = 7.8, 1.5 Hz, 1H), 7.54 (d, J = 7.9 Hz, 1H), 7.49 (s, 1H), 7.46 (d, J = 7.9 Hz, 1H), 7.39 (d, J = 7.9 Hz, 1H), 7.33 (d, J = 1.8 Hz, 1H), 7.27 (dd, J = 7.9, 1.8 Hz, 1H), 7.13 (t, J = 7.8 Hz, 1H), 7.05 (dd, J = 7.8, 1.6 Hz, 1H), 6.96 (s, 1H), 2.59 (s, 3H), 2.32 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.31 (s, 1H), 13.19 (s, 1H), 9.58 (s, 1H), 7.93 (d, J=7.9 Hz, 1H), 7.85 (dd, J=7.8, 1.5 Hz, 1H), 7.82 (dd, J=7.8, 1.5 Hz, 1H), 7.75 (dd, J=10.4, 1.5 Hz, 1H), 7.58 (t, J=7.8 Hz, 1H), 7.54 (d, J=7.9 Hz, 1H), 7.38 (d, J=8.0 Hz, 1H), 7.33 (d, J=1.9 Hz, 1H), 7.27 (dd, J=8.0, 1.9 Hz, 1H, 7.12 (t, J=7.8 Hz, 1H), 6.99 (dd, J=7.8, 1.5 Hz, 1H), 6.95 (s, 1H), 2.32 (s, 3H), 2.31 (s, 3H)。 Example 80 3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-2,3-dihydro-1H-indol-3-yl] -hydrazino } -2-Fluoro-2'-hydroxy-biphenyl-4-carboxylic acid (Compound 180)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.31 (s, 1H), 13.19 (s, 1H), 9.58 (s, 1H), 7.93 (d, J = 7.9 Hz, 1H), 7.85 (dd, J = 7.8, 1.5 Hz, 1H), 7.82 (dd, J = 7.8, 1.5 Hz, 1H), 7.75 (dd, J = 10.4, 1.5 Hz, 1H), 7.58 (t, J = 7.8 Hz, 1H), 7.54 (d, J = 7.9 Hz, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 1.9 Hz, 1H), 7.27 (dd, J = 8.0, 1.9 Hz, 1H, 7.12 (t, J = 7.8 Hz, 1H), 6.99 (dd, J = 7.8, 1.5 Hz, 1H), 6.95 (s, 1H), 2.32 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.36 (s, 1H), 8.00 (dd, J=6.9, 2.1 Hz, 1H), 7.78 (m, 1H), 7.66 (dd, J=7.7, 1.4 Hz, 1H), 7.50 (d, J=9.5 Hz, 1H), 7.41 (m, 1H), 7.39 (d, J=8.1 Hz, 1H), 7.32 (d, J=1.6 Hz, 1H), 7.26 (dd, J=8.1, 1.6 Hz, 1H), 7.14 (t, J=7.7 Hz, 1H), 7.07 (dd, J=7.7, 1.4 Hz, 1H), 6.80 (s, 1H), 2.32 (s, 3H), 2.31 (s, 3H)。 Example 81: 3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -4-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-1H-indole-3- Yl] -hydrazino} -4-fluoro-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 181)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.36 (s, 1H), 8.00 (dd, J = 6.9, 2.1 Hz, 1H), 7.78 (m, 1H), 7.66 (dd, J = 7.7, 1.4 Hz, 1H), 7.50 (d, J = 9.5 Hz, 1H), 7.41 (m, 1H), 7.39 (d, J = 8.1 Hz, 1H), 7.32 (d, J = 1.6 Hz, 1H), 7.26 ( dd, J = 8.1, 1.6 Hz, 1H), 7.14 (t, J = 7.7 Hz, 1H), 7.07 (dd, J = 7.7, 1.4 Hz, 1H), 6.80 (s, 1H), 2.32 (s, 3H ), 2.31 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.38 (s, 1H), 13.22 (s, 1H), 9.78 (s, 1H), 8.01 (dd, J=7.0, 2.3 Hz, 1H), 7.80 (ddd, J=8.6, 4.2, 2.3 Hz, 1H), 7.55 (d, J=2.5 Hz, 1H), 7.51 (d, J=9.5 Hz, 1H), 7.42 (dd, J=10.5, 8.6 Hz, 1H), 7.38 (d, J=8.0 Hz, 1H), 7.31 (d, J=1.6 Hz, 1H), 7.25 (dd, J=8.0, 1.6 Hz, 1H), 7.10 (d, J=2.5 Hz, 1H), 6.80 (s, 1H), 2.32 (s, 3H), 2.30 (s, 3H)。 Example 82: 5′-chloro-3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indole -3-ylidene] -hydrazino} -4-fluoro-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 182)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.38 (s, 1H), 13.22 (s, 1H), 9.78 (s, 1H), 8.01 (dd, J = 7.0, 2.3 Hz, 1H), 7.80 ( ddd, J = 8.6, 4.2, 2.3 Hz, 1H), 7.55 (d, J = 2.5 Hz, 1H), 7.51 (d, J = 9.5 Hz, 1H), 7.42 (dd, J = 10.5, 8.6 Hz, 1H ), 7.38 (d, J = 8.0 Hz, 1H), 7.31 (d, J = 1.6 Hz, 1H), 7.25 (dd, J = 8.0, 1.6 Hz, 1H), 7.10 (d, J = 2.5 Hz, 1H) ), 6.80 (s, 1H), 2.32 (s, 3H), 2.30 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.26 (s, 1H), 13.05 (s, 1H), 9.42 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.95 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.86 (d, J = 7.9 Hz, 1H), 7.81 (dd, J = 7.9, 1.4 Hz, 1H), 7.80 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.77 (dd, J = 7.8, 1.6 Hz, 1H), 7.61 (t, J = 7.7 Hz, 1H), 7.29 (d, J = 1.4 Hz, 1H), 7.18 (s, 1H), 7.16 (s, 2H), 7.14 (t, J = 7.8 Hz, 1H), 7.06 (dd, J = 7.8, 1.6 Hz, 1H), 3.83 (s, 3H), 2.38 (s, 6H)。 Example 83: 3-[(3'-carboxy-2-hydroxy-biphenyl-3-yl) -hydrazono] -1- (3,5-dimethyl-phenyl) -2-oxo-2,3-dihydro-1H -Indole-6-carboxylic acid methyl ester (Compound 183)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.26 (s, 1H), 13.05 (s, 1H), 9.42 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.95 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.86 (d, J = 7.9 Hz, 1H), 7.81 (dd, J = 7.9, 1.4 Hz, 1H), 7.80 (ddd, J = 7.7, 1.6, 1.2 Hz , 1H), 7.77 (dd, J = 7.8, 1.6 Hz, 1H), 7.61 (t, J = 7.7 Hz, 1H), 7.29 (d, J = 1.4 Hz, 1H), 7.18 (s, 1H), 7.16 (s, 2H), 7.14 (t, J = 7.8 Hz, 1H), 7.06 (dd, J = 7.8, 1.6 Hz, 1H), 3.83 (s, 3H), 2.38 (s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.35 (s, 1H), 13.24 (s, 1H), 9.43 (s, 1H), 8.01 (dd, J = 7.2, 2.6 Hz, 1H), 7.85 (d, J = 7.9 Hz, 1H), 7.81 (dd, J = 7.9, 1.3 Hz, 1H), 7.79 (m, 1H), 7.77 (dd, J = 7.8, 1.6 Hz, 1H), 7.42 (dd, J = 10.7, 8.5 Hz, 1H), 7.28 (d, J = 1.3 Hz, 1H), 7.18 (s, 1H), 7.16 (s, 2H), 7.13 (t, J = 7.8 Hz, 1H), 7.05 (dd, J = 7.8, 1.6 Hz, 1H), 3.83 (s, 3H), 2.37 (s, 6H)。 Example 84 3-[(3′-carboxy-4′-fluoro-2-hydroxy-biphenyl-3-yl) -hydrazono] -1- (3,5-dimethyl-phenyl) -2-oxo-2, 3-Dihydro-1H-indole-6-carboxylic acid methyl ester (Compound 184)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.35 (s, 1H), 13.24 (s, 1H), 9.43 (s, 1H), 8.01 (dd, J = 7.2, 2.6 Hz, 1H), 7.85 ( d, J = 7.9 Hz, 1H), 7.81 (dd, J = 7.9, 1.3 Hz, 1H), 7.79 (m, 1H), 7.77 (dd, J = 7.8, 1.6 Hz, 1H), 7.42 (dd, J = 10.7, 8.5 Hz, 1H), 7.28 (d, J = 1.3 Hz, 1H), 7.18 (s, 1H), 7.16 (s, 2H), 7.13 (t, J = 7.8 Hz, 1H), 7.05 (dd , J = 7.8, 1.6 Hz, 1H), 3.83 (s, 3H), 2.37 (s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.34 (s, 1H), 13.24 (s, 1H), 9.43 (s, 1H), 8.01 (dd, J = 7.1, 2.1 Hz, 1H), 7.85 (d, J = 7.9 Hz, 1H), 7.81 (m, 1H), 7.79 (m, 1H), 7.77 (m, 1H), 7.41 (dd, J = 10.5, 8.8 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.32 (d, J = 1.8 Hz, 1H), 7.27 (d, J = 1.0 Hz, 1H), 7.26 (m, 1H), 7.13 (t, J = 7.8 Hz, 1H), 7.05 (dd, J = 7.8, 1.6 Hz, 1H), 3.82 (s, 3H), 2.33 (s, 3H), 2.31 (s, 3H)。 Example 85: 3-[(3′-carboxy-4′-fluoro-2-hydroxy-biphenyl-3-yl) -hydrazono] -1- (3,4-dimethyl-phenyl) -2-oxo-2, 3-Dihydro-1H-indole-6-carboxylic acid methyl ester (Compound 185)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.34 (s, 1H), 13.24 (s, 1H), 9.43 (s, 1H), 8.01 (dd, J = 7.1, 2.1 Hz, 1H), 7.85 ( d, J = 7.9 Hz, 1H), 7.81 (m, 1H), 7.79 (m, 1H), 7.77 (m, 1H), 7.41 (dd, J = 10.5, 8.8 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.32 (d, J = 1.8 Hz, 1H), 7.27 (d, J = 1.0 Hz, 1H), 7.26 (m, 1H), 7.13 (t, J = 7.8 Hz, 1H), 7.05 (dd, J = 7.8, 1.6 Hz, 1H), 3.82 (s, 3H), 2.33 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, CD₃OD- d₄) δ 8.05 (dd, J = 6.7, 1.2 Hz, 1H), 7.89-7.81 (m, 2H), 7.75-7.70 (m, 2H), 7.40 (s, 1H), 7.29 (dd, J = 10.3, 8.7 Hz, 1H), 7.18 (s, 1H), 7.09 (s, 2H), 6.97 (d, J = 1.7 Hz, 1H), 3.86 (s, 3H), 2.41 (s, 6H)。 Example 86: 3-[(3'-carboxy-5-chloro-4'-fluoro-2-hydroxy-biphenyl-3-yl) -hydrazono] -1- (3,5-dimethyl-phenyl) -2- Oxo-2,3-dihydro-1H-indole-6-carboxylic acid methyl ester (compound 186)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, CD ₃ OD- d ₄ ) δ 8.05 (dd, J = 6.7, 1.2 Hz, 1H), 7.89-7.81 (m, 2H), 7.75-7.70 (m, 2H), 7.40 (s , 1H), 7.29 (dd, J = 10.3, 8.7 Hz, 1H), 7.18 (s, 1H), 7.09 (s, 2H), 6.97 (d, J = 1.7 Hz, 1H), 3.86 (s, 3H) , 2.41 (s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, CD₃OD- d₄) δ 8.05 (t, J = 1.5 Hz, 1H), 8.03 (d, J = 5.3 Hz, 1H), 7.89 (ddd, J = 7.7, 1.5, 1.0 Hz, 1H), 7.74 (ddd, J = 7.6, 1.1, 0.6 Hz, 1H), 7.73 (dd, J = 7.8, 1.6 Hz, 1H), 7.56 (ddd, J = 7.7, 1.5, 1.0 Hz, 1H), 7.41 (t, J = 7.7 Hz, 1H), 7.37 (d, J = 5.3 Hz, 1H), 7.28 (td, J = 7.6, 1.1 Hz, 1H), 7.20 (td, J = 7.6, 0.8 Hz, 1H), 7.03 (t, J = 7.8 Hz, 1H), 6.97 (dd, J = 7.8, 1.6 Hz, 1H), 6.93 (ddd, J = 7.8, 0.8, 0.6 Hz, 1H)。 Example 87: 3 ′-{N ′-[1- (2-cyano-thiophen-3-yl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy -Biphenyl-3-carboxylic acid (Compound 187)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, CD ₃ OD- d ₄ ) δ 8.05 (t, J = 1.5 Hz, 1H), 8.03 (d, J = 5.3 Hz, 1H), 7.89 (ddd, J = 7.7, 1.5, 1.0 Hz, 1H), 7.74 (ddd, J = 7.6, 1.1, 0.6 Hz, 1H), 7.73 (dd, J = 7.8, 1.6 Hz, 1H), 7.56 (ddd, J = 7.7, 1.5, 1.0 Hz, 1H) , 7.41 (t, J = 7.7 Hz, 1H), 7.37 (d, J = 5.3 Hz, 1H), 7.28 (td, J = 7.6, 1.1 Hz, 1H), 7.20 (td, J = 7.6, 0.8 Hz, 1H), 7.03 (t, J = 7.8 Hz, 1H), 6.97 (dd, J = 7.8, 1.6 Hz, 1H), 6.93 (ddd, J = 7.8, 0.8, 0.6 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, CD₃OD- d₄) δ 8.15 (t, J = 1.6 Hz, 1H), 7.99 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.74 (dd, J = 7.8, 1.6 Hz, 1H), 7.73 (m, 1H), 7.71 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.65-7.62 (m, 2H), 7.52 (t, J = 7.7 Hz, 1H), 7.33 (dd, J = 3.9, 2.7 Hz, 1H), 7.28 (td, J = 7.6, 1.2 Hz, 1H), 7.18 (td, J = 7.6, 0.8 Hz, 1H), 7.07 (t, J = 7.8 Hz, 1H), 7.04 (d, J = 7.6 Hz, 1H), 6.98 (dd, J = 7.8, 1.6 Hz, 1H)。 Example 88: 2′-hydroxy-3 ′-[N ′-(2-oxo-1-thiophen-3-yl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid Acid (Compound 188)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, CD ₃ OD- d ₄ ) δ 8.15 (t, J = 1.6 Hz, 1H), 7.99 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.74 (dd, J = 7.8 , 1.6 Hz, 1H), 7.73 (m, 1H), 7.71 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.65-7.62 (m, 2H), 7.52 (t, J = 7.7 Hz, 1H) , 7.33 (dd, J = 3.9, 2.7 Hz, 1H), 7.28 (td, J = 7.6, 1.2 Hz, 1H), 7.18 (td, J = 7.6, 0.8 Hz, 1H), 7.07 (t, J = 7.8 Hz, 1H), 7.04 (d, J = 7.6 Hz, 1H), 6.98 (dd, J = 7.8, 1.6 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.25 (s, 1H), 13.05 (s, 1H), 9.42 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.95 (ddd, J = 7.8, 1.6, 1.2 Hz, 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.81 (dd, J = 8.0, 1.4 Hz, 1H), 7.79 (ddd, J = 7.8, 1.6, 1.2 Hz, 1H), 7.77 (dd, J = 7.9, 1.6 Hz, 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.32 (d, J = 2.0 Hz, 1H), 7.28 (d, J = 1.4 Hz, 1H), 7.26 (dd, J = 8.0, 2.0 Hz, 1H), 7.14 (t, J = 7.9 Hz, 1H), 7.06 (dd, J = 7.9, 1.6 Hz, 1H), 3.82 (s, 3H), 2.33 (s, 3H), 2.31 (s, 3H)。 Example 89: 3-[(3′-carboxy-2-hydroxy-biphenyl-3-yl) -hydrazono] -1- (3,4-dimethyl-phenyl) -2-oxo-2,3-dihydro-1H -Indole-6-carboxylic acid methyl ester (Compound 189)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.25 (s, 1H), 13.05 (s, 1H), 9.42 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.95 (ddd, J = 7.8, 1.6, 1.2 Hz, 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.81 (dd, J = 8.0, 1.4 Hz, 1H), 7.79 (ddd, J = 7.8, 1.6, 1.2 Hz , 1H), 7.77 (dd, J = 7.9, 1.6 Hz, 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.32 (d, J = 2.0 Hz , 1H), 7.28 (d, J = 1.4 Hz, 1H), 7.26 (dd, J = 8.0, 2.0 Hz, 1H), 7.14 (t, J = 7.9 Hz, 1H), 7.06 (dd, J = 7.9, 1.6 Hz, 1H), 3.82 (s, 3H), 2.33 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.20 (s, 1H), 13.02 (s, 1H), 9.49 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 8.11 (d, J = 2.4 Hz, 1H), 7.98 (d, J = 8.5 Hz, 1H), 7.95 (ddd, J = 7.7, 1.7, 1.3 Hz, 1H), 7.94 (dd, J = 8.5, 2.4 Hz, 1H), 7.90 (d, J = 7.8 Hz, 1H), 7.79 (dd, J = 7.8, 1.6 Hz, 1H), 7.79 (m, 1H), 7.66 (dd, J = 7.8, 1.3 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.51 (d, J = 1.3 Hz, 1H), 7.15 (t, J = 7.8 Hz, 1H), 7.09 (dd, J = 7.8, 1.6 Hz, 1H)。 Example 90: 3 ′-{N ′-[1- (4-chloro-3-trifluoromethyl-phenyl) -6-cyano-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino } -2'-Hydroxy-biphenyl-3-carboxylic acid (Compound 190)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.20 (s, 1H), 13.02 (s, 1H), 9.49 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 8.11 (d, J = 2.4 Hz, 1H), 7.98 (d, J = 8.5 Hz, 1H), 7.95 (ddd, J = 7.7, 1.7, 1.3 Hz, 1H), 7.94 (dd, J = 8.5, 2.4 Hz, 1H), 7.90 (d, J = 7.8 Hz, 1H), 7.79 (dd, J = 7.8, 1.6 Hz, 1H), 7.79 (m, 1H), 7.66 (dd, J = 7.8, 1.3 Hz, 1H), 7.60 (t , J = 7.7 Hz, 1H), 7.51 (d, J = 1.3 Hz, 1H), 7.15 (t, J = 7.8 Hz, 1H), 7.09 (dd, J = 7.8, 1.6 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.37 (s, 1H), 13.14 (s, 1H), 9.74 (s, 1H), 8.01 (dd, J = 7.0, 2.4 Hz, 1H), 7.99 (d, J = 7.8 Hz, 1H), 7.80 (ddd, J = 8.5, 4.6, 2.4 Hz, 1H), 7.77 (d, J = 2.6 Hz, 1H), 7.64 (dd, J = 7.8, 1.3 Hz, 1H), 7.49 (d, J = 9.1 Hz, 2H), 7.47 (d, J = 9.1 Hz, 2H), 7.42 (dd, J = 10.7, 8.5 Hz, 1H), 7.24 (d, J = 1.3 Hz, 1H), 7.09 (d, J = 2.6 Hz, 1H), 3.01 (sept, J = 6.9 Hz, 1H), 1.28 (d, J = 6.9 Hz, 6H)。 Example 91: 5′-chloro-3 ′-{N ′-[6-cyano-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -4-Fluoro-2'-hydroxy-biphenyl-3-carboxylic acid (Compound 191)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.37 (s, 1H), 13.14 (s, 1H), 9.74 (s, 1H), 8.01 (dd, J = 7.0, 2.4 Hz, 1H), 7.99 ( d, J = 7.8 Hz, 1H), 7.80 (ddd, J = 8.5, 4.6, 2.4 Hz, 1H), 7.77 (d, J = 2.6 Hz, 1H), 7.64 (dd, J = 7.8, 1.3 Hz, 1H ), 7.49 (d, J = 9.1 Hz, 2H), 7.47 (d, J = 9.1 Hz, 2H), 7.42 (dd, J = 10.7, 8.5 Hz, 1H), 7.24 (d, J = 1.3 Hz, 1H ), 7.09 (d, J = 2.6 Hz, 1H), 3.01 (sept, J = 6.9 Hz, 1H), 1.28 (d, J = 6.9 Hz, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, CD₃OD- d₄) δ 7.91 (dd, J = 6.8, 2.4 Hz, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.73 (dd, J = 7.7, 1.6 Hz, 1H), 7.62 (ddd, J = 8.5, 4.6, 2.4 Hz, 1H), 7.48 (d, J = 8.4 Hz, 2H), 7.47 (m, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.21 (dd, J = 10.3, 8.5 Hz, 1H), 7.09 (d, J = 1.0 Hz, 1H), 7.05 (t, J = 7.7 Hz, 1H), 7.00 (dd, J = 7.7, 1.6 Hz, 1H), 3.02 (sept, J = 6.9 Hz, 1H), 1.32 (d, J = 6.9 Hz, 6H)。 Example 92 3 ′-{N ′-[6-cyano-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -4-fluoro- 2'-Hydroxy-biphenyl-3-carboxylic acid (Compound 192)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, CD ₃ OD- d ₄ ) δ 7.91 (dd, J = 6.8, 2.4 Hz, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.73 (dd, J = 7.7, 1.6 Hz, 1H), 7.62 (ddd, J = 8.5, 4.6, 2.4 Hz, 1H), 7.48 (d, J = 8.4 Hz, 2H), 7.47 (m, 1H), 7.40 (d, J = 8.4 Hz, 2H ), 7.21 (dd, J = 10.3, 8.5 Hz, 1H), 7.09 (d, J = 1.0 Hz, 1H), 7.05 (t, J = 7.7 Hz, 1H), 7.00 (dd, J = 7.7, 1.6 Hz) , 1H), 3.02 (sept, J = 6.9 Hz, 1H), 1.32 (d, J = 6.9 Hz, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, CD₃OD- d₄) δ 7.88 (d, J = 7.7 Hz, 1H), 7.78 (d, J = 7.7 Hz, 1H), 7.65 (s, 1H), 7.58 (m, 1H), 7.53-7.44 (m, 3H), 7.37 (d, J = 8.0 Hz, 1H), 7.25 (s, 1H), 7.19 (d, J = 8.0 Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H), 7.01 (d, J = 7.5 Hz, 1H), 6.99 (s, 1H), 5.10 (q, J = 7.0 Hz, 1H), 2.37 (s, 3H), 2.37 (s, 3H)。 Example 93: (±) -1- (3,4-dimethyl-phenyl) -3-{[2-hydroxy-3 '-(2,2,2-trifluoro-1-hydroxy-ethyl) -biphenyl- 3-yl] -hydrazono} -6-methanesulfonyl-1,3-dihydro-indol-2-one (Compound 193)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, CD ₃ OD- d ₄ ) δ 7.88 (d, J = 7.7 Hz, 1H), 7.78 (d, J = 7.7 Hz, 1H), 7.65 (s, 1H), 7.58 (m, 1H), 7.53-7.44 (m, 3H), 7.37 (d, J = 8.0 Hz, 1H), 7.25 (s, 1H), 7.19 (d, J = 8.0 Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H), 7.01 (d, J = 7.5 Hz, 1H), 6.99 (s, 1H), 5.10 (q, J = 7.0 Hz, 1H), 2.37 (s, 3H), 2.37 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, CD₃OD- d₄) δ 8.06 (s, 1H), 7.90 (d, J = 7.8 Hz, 1H), 7.78 (m, 1H), 7.71 (d, J = 7.8 Hz, 1H), 7.62 (m, 1H), 7.44 (m, 2H), 7.40 (d, J = 8.2 Hz, 2H), 7.32 (d, J = 8.2 Hz, 2H), 7.04 (s, 1H), 7.00 (t, J = 7.6 Hz, 1H), 6.95 (d, J = 7.6 Hz, 1H), 2.94 (sept, J = 7.0 Hz, 1H), 1.23 (d, J = 7.0 Hz, 6H)。 Example 94: 3 ′-{N ′-[6-cyano-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy -Biphenyl-3-carboxylic acid (Compound 194)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, CD ₃ OD- d ₄ ) δ 8.06 (s, 1H), 7.90 (d, J = 7.8 Hz, 1H), 7.78 (m, 1H), 7.71 (d, J = 7.8 Hz, 1H), 7.62 (m, 1H), 7.44 (m, 2H), 7.40 (d, J = 8.2 Hz, 2H), 7.32 (d, J = 8.2 Hz, 2H), 7.04 (s, 1H), 7.00 ( t, J = 7.6 Hz, 1H), 6.95 (d, J = 7.6 Hz, 1H), 2.94 (sept, J = 7.0 Hz, 1H), 1.23 (d, J = 7.0 Hz, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.10 (s, 1H), 12.93 (s, 1H), 8.47 (d, J = 2.3 Hz, 1H), 8.16 (dd, J = 8.7, 2.3 Hz, 1H), 8.10 (t, J = 1.6 Hz, 1H), 7.93 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.85 (dd, J = 7.8, 1.7 Hz, 1H), 7.78 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.58 (t, J = 7.7 Hz, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.32-7.21 (m, 2H), 7.12 (t, J = 7.8 Hz, 1H), 7.05 (dd, J = 7.8, 1.7 Hz, 1H), 6.99 (d, J = 8.7 Hz, 1H), 2.30 (s, 3H), 2.28 (s, 3H)。 Example 95: 3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -5-nitro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ′ -Hydroxy-biphenyl-3-carboxylic acid (Compound 195)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.10 (s, 1H), 12.93 (s, 1H), 8.47 (d, J = 2.3 Hz, 1H), 8.16 (dd, J = 8.7, 2.3 Hz, 1H), 8.10 (t, J = 1.6 Hz, 1H), 7.93 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.85 (dd, J = 7.8, 1.7 Hz, 1H), 7.78 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.58 (t, J = 7.7 Hz, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.32-7.21 (m, 2H), 7.12 (t, J = 7.8 Hz, 1H), 7.05 (dd, J = 7.8, 1.7 Hz, 1H), 6.99 (d, J = 8.7 Hz, 1H), 2.30 (s, 3H), 2.28 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, CD₃OD-d₄) δ 8.43 (s, 2H), 8.11 (t, J = 1.2 Hz, 1H), 7.94 (dt, J = 7.6, 1.2 Hz, 1H), 7.71 (dd, J = 7.8, 1.6 Hz, 1H), 7.69 (dd, J = 7.4, 0.9 Hz, 1H), 7.66 (dt, J = 7.6, 1.2 Hz, 1H), 7.47 (t, J = 7.6 Hz, 1H), 7.30 (d, J = 8.1 Hz, 1H), 7.22-7.18 (m, 2H), 7.14 (dd, J = 7.9, 2.0 Hz, 1H), 7.12 (m, 1H), 7.03 (t, J = 7.8 Hz, 1H), 6.94 (dd, J = 7.8, 1.6 Hz, 1H), 6.81 (d, J = 7.8 Hz, 1H), 3.30 (s, 3H), 2.31 (s, 6H)。 Example 96: 3 '-{N'-[1- (3,4-dimethyl-phenyl) -6-methanesulfonyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 '-Hydroxy-biphenyl-3-carboxylic acid (Compound 196)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, CD ₃ OD-d ₄ ) δ 8.43 (s, 2H), 8.11 (t, J = 1.2 Hz, 1H), 7.94 (dt, J = 7.6, 1.2 Hz, 1H), 7.71 (dd , J = 7.8, 1.6 Hz, 1H), 7.69 (dd, J = 7.4, 0.9 Hz, 1H), 7.66 (dt, J = 7.6, 1.2 Hz, 1H), 7.47 (t, J = 7.6 Hz, 1H) , 7.30 (d, J = 8.1 Hz, 1H), 7.22-7.18 (m, 2H), 7.14 (dd, J = 7.9, 2.0 Hz, 1H), 7.12 (m, 1H), 7.03 (t, J = 7.8 Hz, 1H), 6.94 (dd, J = 7.8, 1.6 Hz, 1H), 6.81 (d, J = 7.8 Hz, 1H), 3.30 (s, 3H), 2.31 (s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 8.25 (d, J = 7.8 Hz, 1H), 8.22 (t, J = 1.5 Hz, 1H), 7.87-7.82 (m, 2H), 7.51 (t, J = 7.8 Hz, 1H), 7.41 (dd, J = 7.7, 1.3 Hz, 1H), 7.31-7.26 (m, 2H), 7.22 (d, J = 1.9 Hz, 1H), 7.15 (dd, J = 7.9, 1.9 Hz, 1H), 6.99 (dd, J = 7.6, 1.5 Hz, 1H), 6.92-6.88 (m, 2H), 2.27 (s, 6H)。 Example 97: 3 ′-{N ′-[6-cyano-1- (3,4-dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ′ -Hydroxy-biphenyl-3-carboxylic acid (Compound 197)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 8.25 (d, J = 7.8 Hz, 1H), 8.22 (t, J = 1.5 Hz, 1H), 7.87-7.82 (m, 2H), 7.51 (t, J = 7.8 Hz, 1H), 7.41 (dd, J = 7.7, 1.3 Hz, 1H), 7.31-7.26 (m, 2H), 7.22 (d, J = 1.9 Hz, 1H), 7.15 (dd, J = 7.9 , 1.9 Hz, 1H), 6.99 (dd, J = 7.6, 1.5 Hz, 1H), 6.92-6.88 (m, 2H), 2.27 (s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300 MHz, DMSO-d₆) δ 8.91 (m, 1H), 8.85 (m, 0.5H), 8.72 (m, 0.5H), 8.43 (t, J = 2.0 Hz, 0.5H), 8.30 (t, J = 2.1 Hz, 0.5H), 8.06 (m, 0.5H), 8.02 (t, J = 1.5 Hz, 0.5H), 7.90 (t, J = 1.6 Hz, 0.5H), 7.73 (m, 0.5H), 7.72-7.53 (m, 3H), 7.37 (t, J = 7.6 Hz, 0.5H), 7.30 (t, J = 7.7 Hz, 0.5H), 7.12 (m, 1H), 7.03 (m, 0.5H), 6.95-6.61 (m, 3.5H)。 Example 98: 3 ′-{N ′-[1- (5-cyano-pyridin-3-yl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy -Biphenyl-3-carboxylic acid (Compound 198)

This compound was prepared as described in Scheme II. ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 8.91 (m, 1H), 8.85 (m, 0.5H), 8.72 (m, 0.5H), 8.43 (t, J = 2.0 Hz, 0.5H), 8.30 (t, J = 2.1 Hz, 0.5H), 8.06 (m, 0.5H), 8.02 (t, J = 1.5 Hz, 0.5H), 7.90 (t, J = 1.6 Hz, 0.5H), 7.73 (m, 0.5H), 7.72-7.53 (m, 3H), 7.37 (t, J = 7.6 Hz, 0.5H), 7.30 (t, J = 7.7 Hz, 0.5H), 7.12 (m, 1H), 7.03 (m, 0.5H), 6.95-6.61 (m, 3.5H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, CD₃OD-d₄) δ 8.07 (s, 1H), 7.90 (m, 2H), 7.66-7.59 (m, 4H), 7.42 (t, J = 7.7 Hz, 1H), 7.21 (t, J = 7.6 Hz, 1H), 7.09 (t, J = 7.6 Hz, 1H), 7.01 (d, J = 7.6 Hz, 1H), 6.97 (t, J = 7.6 Hz, 1H), 6.88 (dd, J = 7.6, 1.3 Hz, 1H), 6.74 (dd, J = 2.0, 0.7 Hz, 1H)。 Example 99: 3 ′-[N ′-(1-furan-3-yl-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2′-hydroxy-biphenyl-3-carboxylic acid Acid (Compound 199)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, CD ₃ OD-d ₄ ) δ 8.07 (s, 1H), 7.90 (m, 2H), 7.66-7.59 (m, 4H), 7.42 (t, J = 7.7 Hz, 1H), 7.21 (t, J = 7.6 Hz, 1H), 7.09 (t, J = 7.6 Hz, 1H), 7.01 (d, J = 7.6 Hz, 1H), 6.97 (t, J = 7.6 Hz, 1H), 6.88 ( dd, J = 7.6, 1.3 Hz, 1H), 6.74 (dd, J = 2.0, 0.7 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.02 (s, 1H), 8.09 (t, J = 1.6 Hz, 1H) ,7.92 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.76 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.70 (dd, J = 7.8, 1.6 Hz, 1H), 7.70 (m, 1H), 7.57 (t, J = 7.7 Hz, 1H), 7.27 (td, J = 7.7, 1.1 Hz, 1H), 7.16 (t, J = 7.8 Hz, 1H), 7.13-7.07 (m, 3H), 6.99-6.96 (m, 2H), 6.82 (d, J = 8.1 Hz, 1H), 6.13 (s, 2H)。混合物 〜９０：１０。 Example 100: 3 ′-[N ′-(1-Benzo [1,3] dioxol-5-yl-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2′-hydroxy -Biphenyl-3-carboxylic acid (Compound 200)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.02 (s, 1H), 8.09 (t, J = 1.6 Hz, 1H), 7.92 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.76 ( ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.70 (dd, J = 7.8, 1.6 Hz, 1H), 7.70 (m, 1H), 7.57 (t, J = 7.7 Hz, 1H), 7.27 (td , J = 7.7, 1.1 Hz, 1H), 7.16 (t, J = 7.8 Hz, 1H), 7.13-7.07 (m, 3H), 6.99-6.96 (m, 2H), 6.82 (d, J = 8.1 Hz, 1H), 6.13 (s, 2H). Mixture ~ 90: 10.

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 12.94 (s, 1H), 8.10 (s, 1H), 7.92 (d, J = 7.6 Hz, 1H), 7.79-7.69 (m, 3H), 7.63-7.54 (m, 2H), 7.30 (t, J = 7.6 Hz, 1H), 7.20 (t, J = 7.6 Hz, 1H), 7.14-7.06 (m, 2H), 6.99 (d, J = 7.4 Hz, 1H), 6.73 (d, J = 7.6 Hz, 1H), 2.01 (s, 3H)。 Example 101: 2'-hydroxy-3 '-{N'-[1- (3-methyl-thiophen-2-yl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -Biphenyl-3-carboxylic acid (Compound 201)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 12.94 (s, 1H), 8.10 (s, 1H), 7.92 (d, J = 7.6 Hz, 1H), 7.79-7.69 (m, 3H), 7.63- 7.54 (m, 2H), 7.30 (t, J = 7.6 Hz, 1H), 7.20 (t, J = 7.6 Hz, 1H), 7.14-7.06 (m, 2H), 6.99 (d, J = 7.4 Hz, 1H ), 6.73 (d, J = 7.6 Hz, 1H), 2.01 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300 MHz, DMSO-d₆) δ 12.96 (s, 1H), 9.33 (s, 1H), 8.11 (s, 1H), 7.93 (d, J = 7.6 Hz, 1H), 7.78 (d, J = 7.6 Hz, 1H), 7.74-7.69 (m, 2H), 7.63 (dd, J = 5.5, 1.4 Hz, 1H), 7.58 (t, J = 7.6 Hz, 1H), 7.36-7.28 (m, 2H), 7.25-7.15 (m, 2H), 7.10 (t, J = 7.8 Hz, 1H), 7.08 (d, J = 7.8 Hz, 1H), 7.00 (dd, J = 7.6, 1.2 Hz, 1H),。 Example 102: 2′-hydroxy-3 ′-[N ′-(2-oxo-1-thiophen-2-yl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid Acid (Compound 202)

This compound was prepared as described in Scheme II. ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 12.96 (s, 1H), 9.33 (s, 1H), 8.11 (s, 1H), 7.93 (d, J = 7.6 Hz, 1H), 7.78 (d, J = 7.6 Hz, 1H), 7.74-7.69 (m, 2H), 7.63 (dd, J = 5.5, 1.4 Hz, 1H), 7.58 (t, J = 7.6 Hz, 1H), 7.36-7.28 (m, 2H ), 7.25-7.15 (m, 2H), 7.10 (t, J = 7.8 Hz, 1H), 7.08 (d, J = 7.8 Hz, 1H), 7.00 (dd, J = 7.6, 1.2 Hz, 1H) ,.

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.23 (s, 1H), 13.04 (s, 1H), 9.43 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.95 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.80 (dd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.79 (d, J = 7.6 Hz, 1H), 7.78 (dd, J = 7.9, 1.6 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.55 (d, J = 8.0, 1.1 Hz, 1H), 7.51 (d, J = 8.8 Hz, 2H), 7.48 (d, J = 8.8 Hz, 2H), 7.14 (t, J = 7.9 Hz, 1H), 7.06 (dd, J = 7.9, 1.6 Hz, 1H), 7.00 (d, J = 1.1 Hz, 1H), 3.01 (sept, J = 6.8 Hz, 1H), 1.28 (d, J = 6.8 Hz, 6H)。 Example 103: 2'-hydroxy-3 '-{N'-[1- (4-isopropyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] -hydrazino } -Biphenyl-3-carboxylic acid (Compound 203)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.23 (s, 1H), 13.04 (s, 1H), 9.43 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.95 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.80 (dd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.79 (d, J = 7.6 Hz, 1H), 7.78 ( dd, J = 7.9, 1.6 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.55 (d, J = 8.0, 1.1 Hz, 1H), 7.51 (d, J = 8.8 Hz, 2H), 7.48 (d, J = 8.8 Hz, 2H), 7.14 (t, J = 7.9 Hz, 1H), 7.06 (dd, J = 7.9, 1.6 Hz, 1H), 7.00 (d, J = 1.1 Hz, 1H), 3.01 (sept, J = 6.8 Hz, 1H), 1.28 (d, J = 6.8 Hz, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.23 (s, 1H), 13.04 (s, 1H), 9.43 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.95 (d, J = 7.7, 1.6, 1.2 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.80 (dd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.78 (dd, J = 7.7, 1.5 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.55 (m, 1H), 7.47 (d, J = 8.5 Hz, 2H), 7.44 (d, J = 8.5 Hz, 2H), 7.14 (t, J = 7.7 Hz, 1H), 7.06 (dd, J = 7.7, 1.5 Hz, 1H), 6.98 (m, 1H), 2.67 (t, J=7.4 Hz, 2H), 1.67 (sext, J=7.4 Hz, 2H), 0.95 (t, J=7.4 Hz, 3H)。 Example 104: 2'-hydroxy-3 '-{N'-[2-oxo-1- (4-propyl-phenyl) -6-trifluoromethyl-1,2-dihydro-indole-3-ylidene]- Hydrazino} -biphenyl-3-carboxylic acid (compound 204)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.23 (s, 1H), 13.04 (s, 1H), 9.43 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.95 (d, J = 7.7, 1.6, 1.2 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.80 (dd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.78 (dd, J = 7.7, 1.5 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.55 (m, 1H), 7.47 (d, J = 8.5 Hz, 2H), 7.44 (d, J = 8.5 Hz, 2H), 7.14 (t, J = 7.7 Hz, 1H), 7.06 (dd, J = 7.7, 1.5 Hz, 1H), 6.98 (m, 1H), 2.67 (t, J = 7.4 Hz, 2H), 1.67 (sext, J = 7.4 Hz, 2H), 0.95 (t, J = 7.4 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.15 (s, 1H), 13.03 (s, 1H), 9.40 (s, 1H), 8.11 (t, J = 1.6 Hz, 1H), 7.94 (d, J = 7.7, 1.6, 1.1 Hz, 1H), 7.79 (m, 2H), 7.60 (t, J = 7.7 Hz, 1H), 7.48 (dd, J = 7.8, 2.3 Hz, 1H), 7.41 (dd, J = 8.3, 1.4 Hz, 2H), 7.36 (d, J = 8.3 Hz, 2H), 7.21 (ddd, J = 11.6, 9.7, 2.3 Hz, 1H) 7.13 (t, J = 7.8 Hz, 1H), 7.05 (dd, J = 7.8, 1.3 Hz, 1H), 2.69 (q, J = 7.5 Hz, 2H), 1.24 (t, J = 7.5 Hz, 3H)。 Example 105: 3 ′-{N ′-[1- (4-ethyl-phenyl) -5,7-difluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ′ -Hydroxy-biphenyl-3-carboxylic acid (Compound 205)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.15 (s, 1H), 13.03 (s, 1H), 9.40 (s, 1H), 8.11 (t, J = 1.6 Hz, 1H), 7.94 (d, J = 7.7, 1.6, 1.1 Hz, 1H), 7.79 (m, 2H), 7.60 (t, J = 7.7 Hz, 1H), 7.48 (dd, J = 7.8, 2.3 Hz, 1H), 7.41 (dd, J = 8.3, 1.4 Hz, 2H), 7.36 (d, J = 8.3 Hz, 2H), 7.21 (ddd, J = 11.6, 9.7, 2.3 Hz, 1H) 7.13 (t, J = 7.8 Hz, 1H), 7.05 (dd, J = 7.8, 1.3 Hz, 1H), 2.69 (q, J = 7.5 Hz, 2H), 1.24 (t, J = 7.5 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.16 (s, 1H), 12.99 (s, 1H), 9.40 (s, 1H), 8.11 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.79 (m, 1H), 7.78 (dd, J = 7.8, 1.5 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.47 (dd, J = 7.7, 2.3 Hz, 1H), 7.28 (m, 2H), 7.23-7.17 (m, 1H), 7.13 (t, J = 7.8 Hz, 1H), 7.05 (dd, J = 7.8, 1.5 Hz, 1H), 2.29 (s, 3H), 2.27 (s, 3H)。 Example 106: 3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -5,7-difluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 206)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.16 (s, 1H), 12.99 (s, 1H), 9.40 (s, 1H), 8.11 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.79 (m, 1H), 7.78 (dd, J = 7.8, 1.5 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.47 (dd, J = 7.7, 2.3 Hz, 1H), 7.28 (m, 2H), 7.23-7.17 (m, 1H), 7.13 (t, J = 7.8 Hz, 1H), 7.05 (dd, J = 7.8, 1.5 Hz, 1H), 2.29 (s , 3H), 2.27 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.15 (s, 1H), 13.03 (s, 1H), 9.40 (s, 1H), 8.11 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.79 (m, 2H), 7.60 (t, J = 7.7 Hz, 1H), 7.48 (dd, J = 7.8, 2.4 Hz, 1H), 7.40 (dd, J = 8.3, 1.7 Hz, 2H), 7.34 (d, J = 8.3 Hz, 2H), 7.21 (ddd, J = 11.6, 9.7, 2.4 Hz, 1H), 7.13 (t, J = 7.8 Hz, 1H), 7.05 (dd, J = 7.8, 1.6 Hz, 1H), 2.64 (t, J=7.4 Hz, 2H), 1.65 (sext, J = 7.4 Hz, 2H), 0.93 (t, J = 7.4 Hz, 3H)。 Example 107: 3 ′-{N ′-[5,7-difluoro-2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ′ -Hydroxy-biphenyl-3-carboxylic acid (Compound 207)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.15 (s, 1H), 13.03 (s, 1H), 9.40 (s, 1H), 8.11 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.79 (m, 2H), 7.60 (t, J = 7.7 Hz, 1H), 7.48 (dd, J = 7.8, 2.4 Hz, 1H), 7.40 (dd, J = 8.3, 1.7 Hz, 2H), 7.34 (d, J = 8.3 Hz, 2H), 7.21 (ddd, J = 11.6, 9.7, 2.4 Hz, 1H), 7.13 (t, J = 7.8 Hz, 1H), 7.05 (dd, J = 7.8, 1.6 Hz, 1H), 2.64 (t, J = 7.4 Hz, 2H), 1.65 (sext, J = 7.4 Hz, 2H), 0.93 (t, J = 7.4 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.15 (s, 1H), 13.04 (s, 1H), 9.41 (s, 1H), 8.11 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.1 Hz, 1H), 7.79 (m, 1H), 7.78 (dd, J = 7.8, 1.7 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.48 (dd, J = 7.8, 2.2 Hz, 1H), 7.42 (dd, J = 8.8, 1.4 Hz, 2H), 7.39 (d, J = 8.8 Hz, 2H), 7.21 (ddd, J = 11.8, 9.5, 2.2 Hz, 1H), 7.13 (t, J = 7.8 Hz, 1H), 7.05 (dd, J = 7.8, 1.7 Hz, 1H), 2.98 (sept, J = 6.9 Hz, 1H), 1.26 (d, J = 6.9 Hz, 6H)。 Example 108: 3 ′-{N ′-[5,7-difluoro-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ′ -Hydroxy-biphenyl-3-carboxylic acid (Compound 208)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.15 (s, 1H), 13.04 (s, 1H), 9.41 (s, 1H), 8.11 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.1 Hz, 1H), 7.79 (m, 1H), 7.78 (dd, J = 7.8, 1.7 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.48 (dd, J = 7.8, 2.2 Hz, 1H), 7.42 (dd, J = 8.8, 1.4 Hz, 2H), 7.39 (d, J = 8.8 Hz, 2H), 7.21 (ddd, J = 11.8, 9.5, 2.2 Hz, 1H), 7.13 (t , J = 7.8 Hz, 1H), 7.05 (dd, J = 7.8, 1.7 Hz, 1H), 2.98 (sept, J = 6.9 Hz, 1H), 1.26 (d, J = 6.9 Hz, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.22 (s, 1H), 13.02 (s, 1H), 9.41 (s, 1H), 8.10 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.91 (d, J = 7.9 Hz, 1H), 7.79 (dd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.76 (dd, J = 7.8, 1.5 Hz, 1H), 7.59 (t, J = 7.7 Hz, 1H), 7.52 (m, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.31 (m, 1H), 7.25 (dd, J = 8.0, 1.9 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 7.04 (dd, J = 7.8, 1.5 Hz, 1H), 6.94 (m, 1H), 2.30 (s, 3H), 2.29 (s, 3H)。 Example 109: 3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 209)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.22 (s, 1H), 13.02 (s, 1H), 9.41 (s, 1H), 8.10 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.91 (d, J = 7.9 Hz, 1H), 7.79 (dd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.76 (dd, J = 7.8, 1.5 Hz, 1H), 7.59 (t, J = 7.7 Hz, 1H), 7.52 (m, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.31 (m, 1H), 7.25 (dd, J = 8.0, 1.9 Hz, 1H ), 7.12 (t, J = 7.8 Hz, 1H), 7.04 (dd, J = 7.8, 1.5 Hz, 1H), 6.94 (m, 1H), 2.30 (s, 3H), 2.29 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300MHz, DMSO) δ 13.04 (s, 1H), 12.99 (s, 1H), 9.23 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.6, 1.6, 1.2 Hz, 1H), 7.79 (ddd, J = 7.6, 1.6, 1.2 Hz, 1H), 7.70 (dd, J = 7.8, 1.6 Hz, 1H), 7.63 (d, J = 7.5 Hz, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 2.0 Hz, 1H), 7.22 (dd, J = 8.0, 2.0 Hz, 1H), 7.10 (t, J = 7.8 Hz, 1H), 7.04 (m, 1H), 6.98 (dd, J = 7.8, 1.6 Hz, 1H), 6.67 (m, 1H), 2.61 (q, J = 7.6 Hz, 2H), 2.31 (s, 3H), 2.30 (s, 3H), 1.14 (t, J = 7.6 Hz, 3H)。 Example 110: 3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -6-ethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ′ -Hydroxy-biphenyl-3-carboxylic acid (Compound 210)

This compound was prepared as described in Scheme II. ¹ H NMR (300MHz, DMSO) δ 13.04 (s, 1H), 12.99 (s, 1H), 9.23 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.6, 1.6, 1.2 Hz, 1H), 7.79 (ddd, J = 7.6, 1.6, 1.2 Hz, 1H), 7.70 (dd, J = 7.8, 1.6 Hz, 1H), 7.63 (d, J = 7.5 Hz, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 2.0 Hz, 1H), 7.22 (dd, J = 8.0, 2.0 Hz, 1H), 7.10 (t, J = 7.8 Hz, 1H), 7.04 (m, 1H), 6.98 (dd, J = 7.8, 1.6 Hz, 1H), 6.67 (m, 1H), 2.61 (q, J = 7.6 Hz, 2H ), 2.31 (s, 3H), 2.30 (s, 3H), 1.14 (t, J = 7.6 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300MHz, DMSO) δ 12.85 (s, 1H), 9.16 (s, 1H), 8.09 (t, J = 1.7 Hz, 1H), 7.91 (ddd, J = 7.6, 1.7, 1.2 Hz, 1H), 7.76 (ddd, J = 7.6, 1.7, 1.2 Hz, 1H), 7.66 (dd, J = 7.9, 1.6 Hz, 1H), 7.62 (d, J = 8.4 Hz, 1H), 7.57 (t, J = 7.6 Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 7.28 (d, J = 2.1 Hz, 1H), 7.21 (dd, J = 8.0, 2.1 Hz, 1H), 7.07 (t, J = 7.9 Hz, 1H), 6.93 (dd, J = 7.9, 1.6 Hz, 1H), 6.74 (dd, J = 8.4, 2.2 Hz, 1H), 6.33 (d, J = 2.2 Hz, 1H), 3.73 (s, 3H), 2.29 (s, 3H), 2.28 (s, 3H)。 Example 111: 3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -6-methoxy-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ′ -Hydroxy-biphenyl-3-carboxylic acid (Compound 211)

This compound was prepared as described in Scheme II. ¹ H NMR (300MHz, DMSO) δ 12.85 (s, 1H), 9.16 (s, 1H), 8.09 (t, J = 1.7 Hz, 1H), 7.91 (ddd, J = 7.6, 1.7, 1.2 Hz, 1H) , 7.76 (ddd, J = 7.6, 1.7, 1.2 Hz, 1H), 7.66 (dd, J = 7.9, 1.6 Hz, 1H), 7.62 (d, J = 8.4 Hz, 1H), 7.57 (t, J = 7.6 Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 7.28 (d, J = 2.1 Hz, 1H), 7.21 (dd, J = 8.0, 2.1 Hz, 1H), 7.07 (t, J = 7.9 Hz, 1H), 6.93 (dd, J = 7.9, 1.6 Hz, 1H), 6.74 (dd, J = 8.4, 2.2 Hz, 1H), 6.33 (d, J = 2.2 Hz, 1H), 3.73 (s, 3H ), 2.29 (s, 3H), 2.28 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300MHz, DMSO) δ 13.25 (s, 1H), 13.01 (s, 1H), 9.49 (s, 1H), 8.10 (t, J = 1.7 Hz, 1H), 8.01 (s, 1H), 7.93 (ddd, J = 7.7, 1.7, 1.1 Hz, 1H), 7.83 (dd, J = 7.8, 1.9 Hz, 1H), 7.77 (ddd, J = 7.7, 1.7, 1.1 Hz, 1H), 7.58 (t, J = 7.7 Hz, 1H), 7.36 (d, 8.0 Hz, 1H), 7.31 (d, 2.0 Hz, 1H), 7.25 (dd, J = 8.0, 2.0 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 7.07 (dd, J = 7.8, 1.9 Hz, 1H), 7.02 (s, 1H)。 Example 112: 3 ′-{N ′-[5-chloro-1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -Hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 212)

This compound was prepared as described in Scheme II. ¹ H NMR (300MHz, DMSO) δ 13.25 (s, 1H), 13.01 (s, 1H), 9.49 (s, 1H), 8.10 (t, J = 1.7 Hz, 1H), 8.01 (s, 1H), 7.93 (ddd, J = 7.7, 1.7, 1.1 Hz, 1H), 7.83 (dd, J = 7.8, 1.9 Hz, 1H), 7.77 (ddd, J = 7.7, 1.7, 1.1 Hz, 1H), 7.58 (t, J = 7.7 Hz, 1H), 7.36 (d, 8.0 Hz, 1H), 7.31 (d, 2.0 Hz, 1H), 7.25 (dd, J = 8.0, 2.0 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 7.07 (dd, J = 7.8, 1.9 Hz, 1H), 7.02 (s, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300MHz, DMSO) δ 13.03 (s, 1H), 12.94 (s, 1H), 9.17 (s, 1H), 8.10 (t, J = 1.5 Hz, 1H), 7.93 (d, J = 7.7 Hz, 1H), 7.77 (d, J = 7.7 Hz, 1H), 7.69 (dd, J = 7.8, 1.2 Hz, 1H), 7.58 (t, J = 7.7 Hz, 1H), 7.48 (d, J = 7.5 Hz, 1H), 7.30 (d, J = 7.9 Hz, 1H), 7.20 (d, J = 1.8 Hz, 1H), 7.14 (dd, J = 7.9, 1.8 Hz, 1H), 7.09 (t, J = 7.8 Hz, 1H), 7.02 (d, J = 7.8 Hz, 1H), 6.96 (d, J = 7.5 Hz, 1H), 2.31 (s, 3H), 2.28 (s, 3H), 2.23 (s, 3H), 1.62 (s, 3H)。 Example 113: 3 '-{N'-[1- (3,4-dimethyl-phenyl) -6,7-dimethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (compound 213)

This compound was prepared as described in Scheme II. ¹ H NMR (300MHz, DMSO) δ 13.03 (s, 1H), 12.94 (s, 1H), 9.17 (s, 1H), 8.10 (t, J = 1.5 Hz, 1H), 7.93 (d, J = 7.7 Hz , 1H), 7.77 (d, J = 7.7 Hz, 1H), 7.69 (dd, J = 7.8, 1.2 Hz, 1H), 7.58 (t, J = 7.7 Hz, 1H), 7.48 (d, J = 7.5 Hz , 1H), 7.30 (d, J = 7.9 Hz, 1H), 7.20 (d, J = 1.8 Hz, 1H), 7.14 (dd, J = 7.9, 1.8 Hz, 1H), 7.09 (t, J = 7.8 Hz , 1H), 7.02 (d, J = 7.8 Hz, 1H), 6.96 (d, J = 7.5 Hz, 1H), 2.31 (s, 3H), 2.28 (s, 3H), 2.23 (s, 3H), 1.62 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300MHz, DMSO) δ 13.23 (s, 1H), 12.39 (s, 1H), 9.35 (s, 1H), 7.92 (d, J = 7.9 Hz, 1H), 7.74 (dd, J = 7.8, 1.7 Hz, 1H), 7.55 (d, J = 8.5 Hz, 2H), 7.53 (m, 1H), 7.45 (d, J = 8.5 Hz, 2H), 7.39 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 2.2 Hz, 1H), 7.27 (dd, J = 8.0, 2.2 Hz, 1H), 7.11 (t, J = 7.8 Hz, 1H), 7.03 (dd, J = 7.8, 1.7 Hz, 1H), 6.96 (m, 1H), 2.32 (s, 3H), 2.31 (s, 3H), 1.52 (s, 6H)。 Example 114: 2- (3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene]- Hydrazino} -2'-hydroxy-biphenyl-4-yl) -2-methyl-propionic acid (compound 214)

This compound was prepared as described in Scheme II. ¹ H NMR (300MHz, DMSO) δ 13.23 (s, 1H), 12.39 (s, 1H), 9.35 (s, 1H), 7.92 (d, J = 7.9 Hz, 1H), 7.74 (dd, J = 7.8, 1.7 Hz, 1H), 7.55 (d, J = 8.5 Hz, 2H), 7.53 (m, 1H), 7.45 (d, J = 8.5 Hz, 2H), 7.39 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 2.2 Hz, 1H), 7.27 (dd, J = 8.0, 2.2 Hz, 1H), 7.11 (t, J = 7.8 Hz, 1H), 7.03 (dd, J = 7.8, 1.7 Hz, 1H) 6.96 (m, 1H), 2.32 (s, 3H), 2.31 (s, 3H), 1.52 (s, 6H).

これらの化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300MHz, DMSO) δ 13.23 (s, 1H), 12.36 (s, 1H), 9.34 (s, 1H), 7.92 (d, J = 7.9 Hz, 1H), 7.74 (dd, J = 7.8, 1.6 Hz, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.53 (m, 1H), 7.39 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.2 Hz, 1H), 7.33 (d, J = 2.0 Hz, 1H), 7.27 (dd, J = 8.2, 2.0 Hz, 1H), 7.11 (t, J = 7.8 Hz, 1H), 7.02 (dd, J = 7.8, 1.6 Hz, 1H), 6.96 (m, 1H), 3.73 (q, J = 7.0 Hz, 1H), 2.32 (s, 3H), 2.31 (s, 3H), 1.40 (d, J = 7.0 Hz, 3H)。 Example 115: (-)-2- (3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3 -Ilidene] -hydrazino} -2'-hydroxy-biphenyl-4-yl) -propionic acid (compound 215), and (+)-2- (3 '-{N'-[1- (3,4-dimethyl) -Phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-4-yl) -propionic acid (compound 215a)

These compounds were prepared as described in Scheme II. ¹ H NMR (300MHz, DMSO) δ 13.23 (s, 1H), 12.36 (s, 1H), 9.34 (s, 1H), 7.92 (d, J = 7.9 Hz, 1H), 7.74 (dd, J = 7.8, 1.6 Hz, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.53 (m, 1H), 7.39 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.2 Hz, 1H), 7.33 (d, J = 2.0 Hz, 1H), 7.27 (dd, J = 8.2, 2.0 Hz, 1H), 7.11 (t, J = 7.8 Hz, 1H), 7.02 (dd, J = 7.8, 1.6 Hz, 1H) 6.96 (m, 1H), 3.73 (q, J = 7.0 Hz, 1H), 2.32 (s, 3H), 2.31 (s, 3H), 1.40 (d, J = 7.0 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300MHz, DMSO) δ 13.21 (s, 1H), 12.34 (s, 1H), 9.07 (s, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 1.6 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.52 (d, J = 8.3 Hz, 2H), 7.38 (d, J = 8.0 Hz, 1H), 7.37 (d, J = 8.3 Hz, 2H), 7.33 (d, J = 2.0 Hz, 1H), 7.27 (dd, J = 8.0, 2.0 Hz, 1H), 6.96 (m, 1H), 6.85 (d, J = 1.6 Hz, 1H), 3.73 (q, J = 7.0 Hz, 1H), 2.35 (s, 3H), 2.32 (s, 3H), 2.31 (s, 3H), 1.40 (d, J = 7.0 Hz, 3H)。 Example 116: (±)-(3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] ] -Hydrazino} -2'-hydroxy-5'-methyl-biphenyl-4-yl) -propionic acid (Compound 216)

This compound was prepared as described in Scheme II. ¹ H NMR (300MHz, DMSO) δ 13.21 (s, 1H), 12.34 (s, 1H), 9.07 (s, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 1.6 Hz , 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.52 (d, J = 8.3 Hz, 2H), 7.38 (d, J = 8.0 Hz, 1H), 7.37 (d, J = 8.3 Hz, 2H ), 7.33 (d, J = 2.0 Hz, 1H), 7.27 (dd, J = 8.0, 2.0 Hz, 1H), 6.96 (m, 1H), 6.85 (d, J = 1.6 Hz, 1H), 3.73 (q , J = 7.0 Hz, 1H), 2.35 (s, 3H), 2.32 (s, 3H), 2.31 (s, 3H), 1.40 (d, J = 7.0 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300MHz, DMSO) δ 13.13 (s, 1H), 12.37 (s, 1H), 9.26 (s, 1H), 7.99 (d, J = 7.8 Hz, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.55 (m, 1H), 7.53 (dd, J = 9.7, 3.1 Hz, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.39 (m, 1H), 7.33 (d, J = 2.0 Hz, 1H), 7.27 (dd, J = 7.9, 2.0 Hz, 1H), 6.96 (m, 1H), 6.86 (dd, J = 9.4, 3.1 Hz, 1H), 3.74 (q, J = 7.1 Hz, 1H), 2.32 (s, 3H), 2.31 (s, 3H) 1.40 (d, J = 7.1 Hz, 3H)。 Example 117: (±) -2- (3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3] -Ilidene] -hydrazino} -5'-fluoro-2'-hydroxy-biphenyl-4-yl) -propionic acid (Compound 217)

This compound was prepared as described in Scheme II. ¹ H NMR (300MHz, DMSO) δ 13.13 (s, 1H), 12.37 (s, 1H), 9.26 (s, 1H), 7.99 (d, J = 7.8 Hz, 1H), 7.57 (d, J = 8.4 Hz , 2H), 7.55 (m, 1H), 7.53 (dd, J = 9.7, 3.1 Hz, 1H), 7.40 (d, J = 8.4 Hz, 2H), 7.39 (m, 1H), 7.33 (d, J = 2.0 Hz, 1H), 7.27 (dd, J = 7.9, 2.0 Hz, 1H), 6.96 (m, 1H), 6.86 (dd, J = 9.4, 3.1 Hz, 1H), 3.74 (q, J = 7.1 Hz, 1H), 2.32 (s, 3H), 2.31 (s, 3H) 1.40 (d, J = 7.1 Hz, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (300MHz, DMSO) δ 13.03 (s, 1H), 12.56 (s, 1H), 10.86 (s, 1H), 7.80 (d, J = 8.4 Hz, 1H), 7.68 (s, 1H), 7.46 (dd, J = 7.6, 2.3 Hz, 1H), 7.30-7.18 (m, 5H), 7.14 (d, J = 1.6 Hz, 1H), 2.30 (s, 3H), 2.28 (s, 3H)。 Example 118: 5- (4- {N '-[1- (3,4-dimethyl-phenyl) -5,7-difluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino } -3-Hydroxy-benzylidene) -thiazolidine-2,4-dione (Compound 218)

This compound was prepared as described in Scheme V. ¹ H NMR (300MHz, DMSO) δ 13.03 (s, 1H), 12.56 (s, 1H), 10.86 (s, 1H), 7.80 (d, J = 8.4 Hz, 1H), 7.68 (s, 1H), 7.46 (dd, J = 7.6, 2.3 Hz, 1H), 7.30-7.18 (m, 5H), 7.14 (d, J = 1.6 Hz, 1H), 2.30 (s, 3H), 2.28 (s, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.03 (s, 1H), 12.56 (s, 1H), 10.87 (s, 1H), 7.80 (d, J = 8.3 Hz, 1H), 7.68 (s, 1H), 7.47 (dd, J = 7.5, 1.8 Hz, 1H), 7.41 (d, J = 8.2 Hz, 2H), 7.36 (d, J = 8.2 Hz, 2H), 7.27-7.21 (m, 2H), 7.14 (s, 1H), 2.70 (q, J = 7.6 Hz, 2H), 1.24 (t, J = 7.6 Hz, 3H)。 Example 119: 5- (4- {N '-[1- (4-ethyl-phenyl) -5,7-difluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino}- 3-Hydroxy-benzylidene) -thiazolidine-2,4-dione (Compound 219)

This compound was prepared as described in Scheme V. ¹ H NMR (500MHz, DMSO) δ 13.03 (s, 1H), 12.56 (s, 1H), 10.87 (s, 1H), 7.80 (d, J = 8.3 Hz, 1H), 7.68 (s, 1H), 7.47 (dd, J = 7.5, 1.8 Hz, 1H), 7.41 (d, J = 8.2 Hz, 2H), 7.36 (d, J = 8.2 Hz, 2H), 7.27-7.21 (m, 2H), 7.14 (s, 1H), 2.70 (q, J = 7.6 Hz, 2H), 1.24 (t, J = 7.6 Hz, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.03 (s, 1H), 12.56 (s, 1H), 10.87 (s, 1H), 7.80 (d, J = 8.3 Hz, 1H), 7.69 (s, 1H), 7.46 (dd, J = 7.7, 2.3 Hz, 1H), 7.40 (d, J = 8.2 Hz, 2H), 7.34 (d, J = 8.2 Hz, 2H), 7.26-7.20 (m, 2H), 7.14 (d, J = 1.6 Hz, 1H), 2.64 (t, J = 7.4 Hz, 2H), 1.65 (q, J = 7.4 Hz, 2H), 0.93 (t, J = 7.4 Hz, 3H)。 Example 120: 5- (4- {N '-[5,7-difluoro-2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino}- 3-Hydroxy-benzylidene) -thiazolidine-2,4-dione (Compound 220)

This compound was prepared as described in Scheme V. ¹ H NMR (500MHz, DMSO) δ 13.03 (s, 1H), 12.56 (s, 1H), 10.87 (s, 1H), 7.80 (d, J = 8.3 Hz, 1H), 7.69 (s, 1H), 7.46 (dd, J = 7.7, 2.3 Hz, 1H), 7.40 (d, J = 8.2 Hz, 2H), 7.34 (d, J = 8.2 Hz, 2H), 7.26-7.20 (m, 2H), 7.14 (d, J = 1.6 Hz, 1H), 2.64 (t, J = 7.4 Hz, 2H), 1.65 (q, J = 7.4 Hz, 2H), 0.93 (t, J = 7.4 Hz, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.13 (s, 1H), 12.57 (s, 1H), 10.89 (s, 1H), 7.92 (d, J = 7.8 Hz, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.69 (s, 1H), 7.55 (d, J = 7.8 Hz, 1H), 7.51 (d, J = 8.6 Hz, 2H), 7.48 (d, J = 8.6 Hz, 2H), 7.25 (dd, J = 8.4, 1.6 Hz, 1H), 7.16 (d, J = 1.6 Hz, 1H), 6.99 (s, 1H), 3.02 (sept, J = 6.9 Hz, 1H), 1.28 (d, J = 6.9 Hz, 6H)。 Example 121: 5- (3-hydroxy-4- {N '-[1- (4-isopropyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -Hydrazino} -benzylidene) -thiazolidine-2,4-dione (compound 221)

This compound was prepared as described in Scheme V. ¹ H NMR (500MHz, DMSO) δ 13.13 (s, 1H), 12.57 (s, 1H), 10.89 (s, 1H), 7.92 (d, J = 7.8 Hz, 1H), 7.81 (d, J = 8.4 Hz , 1H), 7.69 (s, 1H), 7.55 (d, J = 7.8 Hz, 1H), 7.51 (d, J = 8.6 Hz, 2H), 7.48 (d, J = 8.6 Hz, 2H), 7.25 (dd , J = 8.4, 1.6 Hz, 1H), 7.16 (d, J = 1.6 Hz, 1H), 6.99 (s, 1H), 3.02 (sept, J = 6.9 Hz, 1H), 1.28 (d, J = 6.9 Hz , 6H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.05 (s, 1H), 12.56 (s, 1H), 10.87 (s, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.69 (s, 1H), 7.48 (dd, J = 7.7, 2.1 Hz, 1H), 7.42 (d, J = 8.4 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 7.27-7.21 (m, 2H), 7.15 (d, J = 1.6 Hz, 1H), 2.99 (sept, J = 7.0 Hz, 1H), 1.26 (d, J = 7.0 Hz, 6H)。 Example 122: 5- (3-hydroxy-4- {N '-[1- (4-isopropyl-phenyl) -2-oxo-5,7-difluoro-1,2-dihydro-indole-3-ylidene] -Hydrazino} -benzylidene) -thiazolidine-2,4-dione (compound 222)

This compound was prepared as described in Scheme V. ¹ H NMR (500MHz, DMSO) δ 13.05 (s, 1H), 12.56 (s, 1H), 10.87 (s, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.69 (s, 1H), 7.48 (dd, J = 7.7, 2.1 Hz, 1H), 7.42 (d, J = 8.4 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 7.27-7.21 (m, 2H), 7.15 (d, J = 1.6 Hz, 1H), 2.99 (sept, J = 7.0 Hz, 1H), 1.26 (d, J = 7.0 Hz, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.14 (s, 1H), 13.08 (s, 1H), 9.35 (s, 1H), 8.15 (m, 1H), 8.00 (d, J = 7.8 Hz, 1H), 7.96 (dd, J = 7.7, 1.2 Hz, 1H), 7.82 (m, 1H), 7.61 (t, J = 7.7 Hz, 1H), 7.57 (dd, J=9.2, 3.0 Hz, 1H), 7.55 (d, J = 7.7 Hz, 1H), 7.39 (d, J = 8.1 Hz, 1H), 7.33 (d, J = 1.5 Hz, 1H), 7.27 (dd, J = 8.1, 1.5 Hz, 1H), 6.95 (s, 1H), 6.92 (dd, J = 9.2, 3.0 Hz, 1H), 2.32 (s, 3H), 2.31 (s, 3H)。 Example 123: 3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 5′-Fluoro-2′-hydroxy-biphenyl-3-carboxylic acid (Compound 223)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.14 (s, 1H), 13.08 (s, 1H), 9.35 (s, 1H), 8.15 (m, 1H), 8.00 (d, J = 7.8 Hz, 1H), 7.96 (dd, J = 7.7, 1.2 Hz, 1H), 7.82 (m, 1H), 7.61 (t, J = 7.7 Hz, 1H), 7.57 (dd, J = 9.2, 3.0 Hz, 1H), 7.55 (d, J = 7.7 Hz, 1H), 7.39 (d, J = 8.1 Hz, 1H), 7.33 (d, J = 1.5 Hz, 1H), 7.27 (dd, J = 8.1, 1.5 Hz, 1H), 6.95 (s, 1H), 6.92 (dd, J = 9.2, 3.0 Hz, 1H), 2.32 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.12 (s, 1H), 13.09 (s, 1H), 9.68 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 8.02 (d, J = 7.8 Hz, 1H), 7.97 (ddd, J = 7.7, 1.7, 1.1 Hz, 1H), 7.81 (ddd, J = 7.7, 1.7, 1.1 Hz, 1H), 7.76 (d, J = 2.6 Hz, 1H), 7.61 (t, J = 7.7 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 2.0 Hz, 1H), 7.27 (dd, J = 8.0, 2.0 Hz, 1H), 7.08 (d, J = 2.6 Hz, 1H), 6.95 (s, 1H), 2.32 (s, 3H), 2.31 (s, 3H)。 Example 124: 5'-chloro-3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene ] -Hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (compound 224)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.12 (s, 1H), 13.09 (s, 1H), 9.68 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 8.02 (d, J = 7.8 Hz , 1H), 7.97 (ddd, J = 7.7, 1.7, 1.1 Hz, 1H), 7.81 (ddd, J = 7.7, 1.7, 1.1 Hz, 1H), 7.76 (d, J = 2.6 Hz, 1H), 7.61 ( t, J = 7.7 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 2.0 Hz, 1H), 7.27 (dd, J = 8.0, 2.0 Hz, 1H), 7.08 (d, J = 2.6 Hz, 1H), 6.95 (s, 1H), 2.32 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.22 (s, 1H), 13.04 (s, 1H), 9.16 (s, 1H), 8.11 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.79 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.61 (d, J = 1.9 Hz, 1H), 7.59 (t, J = 7.7 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 1.9 Hz, 1H), 7.27 (dd, J = 8.0, 1.9 Hz, 1H), 6.96 (s, 1H), 6.89 (d, J = 1.9 Hz, 1H), 2.37 (s, 3H), 2.32 (s, 3H), 2.31 (s, 3H)。 Example 125: 3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-5'-methyl-biphenyl-3-carboxylic acid (compound 225)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.22 (s, 1H), 13.04 (s, 1H), 9.16 (s, 1H), 8.11 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.79 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.61 (d, J = 1.9 Hz, 1H), 7.59 ( t, J = 7.7 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 1.9 Hz, 1H), 7.27 (dd, J = 8.0, 1.9 Hz, 1H), 6.96 (s, 1H), 6.89 (d, J = 1.9 Hz, 1H), 2.37 (s, 3H), 2.32 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.20 (s, 1H), 13.06 (s, 1H), 9.48 (s, 1H), 8.12 (m, 1H), 8.01 (d, J = 8.4 Hz, 2H), 7.98-7.94 (m, 2H), 7.86 (d, J = 8.4 Hz, 2H), 7.81-7.78 (m, 2H), 7.61 (t, J = 7.7 Hz, 1H), 7.59 (d, J = 7.5 Hz, 1H), 7.20 (s, 1H), 7.15 (t, J = 7.8 Hz, 1H), 7.08 (dd, J = 7.8, 1.2 Hz, 1H)。 Example 126: 2′-hydroxy-3 ′-{N ′-[2-oxo-6-trifluoromethyl 1- (4-trifluoromethyl-phenyl) -1,2-dihydro-indole-3-ylidene] -Hydrazino} -biphenyl-3-carboxylic acid (Compound 226)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.20 (s, 1H), 13.06 (s, 1H), 9.48 (s, 1H), 8.12 (m, 1H), 8.01 (d, J = 8.4 Hz, 2H), 7.98 -7.94 (m, 2H), 7.86 (d, J = 8.4 Hz, 2H), 7.81-7.78 (m, 2H), 7.61 (t, J = 7.7 Hz, 1H), 7.59 (d, J = 7.5 Hz, 1H), 7.20 (s, 1H), 7.15 (t, J = 7.8 Hz, 1H), 7.08 (dd, J = 7.8, 1.2 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.24 (s, 1H), 13.05 (s, 1H), 9.43 (s, 1H), 8.12 (m, 1H), 7.96-7.91 (m, 2H), 7.81-7.77 (m, 2H), 7.61 (t, J = 7.7 Hz, 1H), 7.54 (d, J = 8.0 Hz, 1H), 7.40 (d, J = 7.9 Hz, 1H), 7.34-7.30 (m, 2H), 7.14 (t, J = 7.8 Hz, 1H), 7.06 (d, J = 7.8 Hz, 1H), 6.97 (s, 1H), 2.69 (q, J = 7.5 Hz, 2H), 2.35 (s, 3H), 1.23 (t, J = 7.5 Hz, 3H)。 Example 127: 3 ′-{N ′-[1- (4-ethyl-3-methyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino } -2'-Hydroxy-biphenyl-3-carboxylic acid (Compound 227)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.24 (s, 1H), 13.05 (s, 1H), 9.43 (s, 1H), 8.12 (m, 1H), 7.96-7.91 (m, 2H), 7.81-7.77 ( m, 2H), 7.61 (t, J = 7.7 Hz, 1H), 7.54 (d, J = 8.0 Hz, 1H), 7.40 (d, J = 7.9 Hz, 1H), 7.34-7.30 (m, 2H), 7.14 (t, J = 7.8 Hz, 1H), 7.06 (d, J = 7.8 Hz, 1H), 6.97 (s, 1H), 2.69 (q, J = 7.5 Hz, 2H), 2.35 (s, 3H), 1.23 (t, J = 7.5 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.16 (s, 1H), 13.05 (s, 1H), 9.48 (s, 1H), 8.14 (d, J = 2.1 Hz, 1H), 8.12 (t, J = 1.5 Hz, 1H), 8.01-7.93 (m, 4H), 7.81-7.78 (m, 2H), 7.61 (t, J = 7.7 Hz, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.23 (s, 1H), 7.15 (t, J = 7.7 Hz, 1H), 7.08 (dd, J = 7.7, 1.3 Hz, 1H)。 Example 128: 3 ′-{N ′-[1- (4-chloro-3-trifluoromethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -Hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 228)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.16 (s, 1H), 13.05 (s, 1H), 9.48 (s, 1H), 8.14 (d, J = 2.1 Hz, 1H), 8.12 (t, J = 1.5 Hz , 1H), 8.01-7.93 (m, 4H), 7.81-7.78 (m, 2H), 7.61 (t, J = 7.7 Hz, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.23 (s, 1H), 7.15 (t, J = 7.7 Hz, 1H), 7.08 (dd, J = 7.7, 1.3 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.14 (s, 1H), 13.09 (s, 1H), 9.35 (s, 1H), 8.16 (t, J = 1.6 Hz, 1H), 8.00 (d, J = 7.9 Hz, 1H), 7.97 (ddd, J = 7.8, 1.6, 1.0 Hz, 1H), 7.82 (ddd, J = 7.8, 1.6, 1.0 Hz, 1H), 7.62 (t, J = 7.8 Hz, 1H), 7.57 (dd, J = 9.5, 3.1 Hz, 1H), 7.56 (m, 1H), 7.17 (s, 1H), 7.16 (s, 2H), 6.98 (s, 1H), 6.92 (dd, J = 9.3, 3.1 Hz, 1H), 2.37 (s, 6H)。 Example 129: 3 ′-{N ′-[1- (3,5-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 5′-Fluoro-2′-hydroxy-biphenyl-3-carboxylic acid (Compound 229)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.14 (s, 1H), 13.09 (s, 1H), 9.35 (s, 1H), 8.16 (t, J = 1.6 Hz, 1H), 8.00 (d, J = 7.9 Hz , 1H), 7.97 (ddd, J = 7.8, 1.6, 1.0 Hz, 1H), 7.82 (ddd, J = 7.8, 1.6, 1.0 Hz, 1H), 7.62 (t, J = 7.8 Hz, 1H), 7.57 ( dd, J = 9.5, 3.1 Hz, 1H), 7.56 (m, 1H), 7.17 (s, 1H), 7.16 (s, 2H), 6.98 (s, 1H), 6.92 (dd, J = 9.3, 3.1 Hz , 1H), 2.37 (s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.37 (s, 1H), 13.11 (s, 1H), 9.35 (s, 1H), 8.04 (dd, J = 1.5, 7.0 Hz, 1H), 7.98 (d, J = 7.5 Hz, 1H), 7.82-7.79 (m, 1H), 7.56-7.53 (m, 2H), 7.41 (t, J = 10.5 Hz, 1H), 7.37 (d, J = 8.5 Hz, 1H), 7.31 (s, 1H), 7.26 (d, J = 8 Hz, 1H), 6.94 (s, 1H), 6.91 (dd, J = 2.5, 9.5 Hz, 1H), 2.29 (s, 6H)。 Example 130: 3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 4,5′-Difluoro-2′-hydroxy-biphenyl-3-carboxylic acid (Compound 230)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.37 (s, 1H), 13.11 (s, 1H), 9.35 (s, 1H), 8.04 (dd, J = 1.5, 7.0 Hz, 1H), 7.98 (d, J = 7.5 Hz, 1H), 7.82-7.79 (m, 1H), 7.56-7.53 (m, 2H), 7.41 (t, J = 10.5 Hz, 1H), 7.37 (d, J = 8.5 Hz, 1H), 7.31 ( s, 1H), 7.26 (d, J = 8 Hz, 1H), 6.94 (s, 1H), 6.91 (dd, J = 2.5, 9.5 Hz, 1H), 2.29 (s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.37 (s, 1H), 13.11 (s, 1H), 9.35 (s, 1H), 8.04 (dd, J = 1.5, 7.0 Hz, 1H), 7.98 (d, J = 7.5 Hz, 1H), 7.82-7.79 (m, 1H), 7.56-7.53 (m, 2H), 7.41 (t, J = 10.5 Hz, 1H), 7.16 (s, 1H), 7.15 (s, 1H), 6.96 (s, 1H), 6.91 (dd, J = 2.5, 9.5 Hz, 1H), 2.35 (s, 6H)。 Example 131: 3 '-{N'-[1- (3,5-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 4,5′-Difluoro-2′-hydroxy-biphenyl-3-carboxylic acid (Compound 231)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.37 (s, 1H), 13.11 (s, 1H), 9.35 (s, 1H), 8.04 (dd, J = 1.5, 7.0 Hz, 1H), 7.98 (d, J = 7.5 Hz, 1H), 7.82-7.79 (m, 1H), 7.56-7.53 (m, 2H), 7.41 (t, J = 10.5 Hz, 1H), 7.16 (s, 1H), 7.15 (s, 1H), 6.96 (s, 1H), 6.91 (dd, J = 2.5, 9.5 Hz, 1H), 2.35 (s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.37 (s, 1H), 13.07 (s, 1H), 9.39 (s, 1H), 8.04 (dd, J = 1.5, 7.0 Hz, 1H), 7.97 (d, J = 9.0 Hz, 1H), 7.82-7.79 (m, 1H), 7.59-7.56 (m, 2H), 7.42 (t, J = 9.5 Hz, 1H), 7.18 (s, 1H), 6.92 (dd, J = 3.0, 9.5 Hz, 1H)。 Example 132: 4,5'-difluoro-2'-hydroxy-3 '-{N'-[2-oxo-6-trifluoromethyl 1- (4-trifluoromethyl-phenyl) -1,2-dihydro -Indol-3-ylidene] -hydrazino} -biphenyl-3-carboxylic acid (Compound 232)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.37 (s, 1H), 13.07 (s, 1H), 9.39 (s, 1H), 8.04 (dd, J = 1.5, 7.0 Hz, 1H), 7.97 (d, J = 9.0 Hz, 1H), 7.82-7.79 (m, 1H), 7.59-7.56 (m, 2H), 7.42 (t, J = 9.5 Hz, 1H), 7.18 (s, 1H), 6.92 (dd, J = 3.0 , 9.5 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.20 (s, 1H), 13.04 (s, 1H), 9.42 (s, 1H), 8.10 (s, 1H), 7.94-7.89 (m, 2H), 7.79-7.75 (m, 2H), 7.59 (t, J = 13 Hz, 1H), 7.52 (d, J = 13.5 Hz, 1H), 7.30 (d, J = 10.5 Hz, 1H), 7.12 (t, J = 13 Hz, 1H), 7.04 (dd, J = 2.0, 12.5 Hz, 1H), 6.98 (s, 1H), 2.29 (s, 6H)。 Example 133: 3 '-{N'-[1- (4-fluoro-3,5-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -Hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 233)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.20 (s, 1H), 13.04 (s, 1H), 9.42 (s, 1H), 8.10 (s, 1H), 7.94-7.89 (m, 2H), 7.79-7.75 ( m, 2H), 7.59 (t, J = 13 Hz, 1H), 7.52 (d, J = 13.5 Hz, 1H), 7.30 (d, J = 10.5 Hz, 1H), 7.12 (t, J = 13 Hz, 1H), 7.04 (dd, J = 2.0, 12.5 Hz, 1H), 6.98 (s, 1H), 2.29 (s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.21 (s, 1H), 13.04 (s, 1H), 9.41 (s, 1H), 8.10 (s, 1H), 7.92 (dd, J = 7.5, 12 Hz, 2H), 7.77 (t, J = 7.5 Hz, 2H), 7.59 (t, J = 7.5 Hz, 1H), 7.52 (d, J = 7.5 Hz, 1H), 7.47 (d, J = 8.5 Hz, 2H), 7.16 (d, J = 8.5 Hz, 2H), 7.12 (d, J = 8.0 Hz, 1H), 7.05 (dd, J = 1.0, 8.0 Hz , 1H), 6.92 (s, 1H), 3.84 (s, 3H)。 Example 134: 2'-hydroxy-3 '-{N'-[1- (4-methoxy-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene]- Hydrazino} -biphenyl-3-carboxylic acid (compound 234)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.21 (s, 1H), 13.04 (s, 1H), 9.41 (s, 1H), 8.10 (s, 1H), 7.92 (dd, J = 7.5, 12 Hz, 2H) , 7.77 (t, J = 7.5 Hz, 2H), 7.59 (t, J = 7.5 Hz, 1H), 7.52 (d, J = 7.5 Hz, 1H), 7.47 (d, J = 8.5 Hz, 2H), 7.16 (d, J = 8.5 Hz, 2H), 7.12 (d, J = 8.0 Hz, 1H), 7.05 (dd, J = 1.0, 8.0 Hz, 1H), 6.92 (s, 1H), 3.84 (s, 3H) .

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.19 (s, 1H), 13.04 (s, 1H), 9.43 (s, 1H), 8.10 (s, 1H), 7.93 (t, J = 6.0 Hz, 2H), 7.78 (t, J = 6.0 Hz, 2H), 7.65-7.62 (m, 2H), 7.59 (t, J = 7.0 Hz, 1H), 7.54 (d, J = 8.5 Hz, 1H), 7.46 (d, J = 8.5 Hz, 2H), 7.13 (t, J = 8.0 Hz, 1H), 7.05 (dd, J = 1.5, 8.0 Hz, 1H), 6.99 (s, 1H)。 Example 135: 3 ′-{N ′-[1- (4-fluoro-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ′ -Hydroxy-biphenyl-3-carboxylic acid (compound 235)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.19 (s, 1H), 13.04 (s, 1H), 9.43 (s, 1H), 8.10 (s, 1H), 7.93 (t, J = 6.0 Hz, 2H), 7.78 (t, J = 6.0 Hz, 2H), 7.65-7.62 (m, 2H), 7.59 (t, J = 7.0 Hz, 1H), 7.54 (d, J = 8.5 Hz, 1H), 7.46 (d, J = 8.5 Hz, 2H), 7.13 (t, J = 8.0 Hz, 1H), 7.05 (dd, J = 1.5, 8.0 Hz, 1H), 6.99 (s, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.21 (s, 1H), 13.04 (s, 1H), 9.44 (s, 1H), 8.11 (s, 1H), 7.92 (dd, J = 8.0, 10.5 Hz, 2H), 7.78 (t, J = 7.5 Hz, 2H), 7.59 (t, J = 7.5 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.13 (t, J = 8.0 Hz, 1H), 7.06-7.04 (m, 2H), 6.73 (s, 2H), 6.66 (s, 1H), 3.79 (s, 6H)。 Example 136: 3 '-{N'-[1- (3,5-dimethoxy-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 236)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.21 (s, 1H), 13.04 (s, 1H), 9.44 (s, 1H), 8.11 (s, 1H), 7.92 (dd, J = 8.0, 10.5 Hz, 2H) , 7.78 (t, J = 7.5 Hz, 2H), 7.59 (t, J = 7.5 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.13 (t, J = 8.0 Hz, 1H), 7.06 -7.04 (m, 2H), 6.73 (s, 2H), 6.66 (s, 1H), 3.79 (s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.23 (s, 1H), 13.04 (s, 1H), 9.42 (s, 1H), 8.11 (s, 1H), 7.92 (dd, J = 7.5, 14.0 Hz, 2H), 7.78 (t, J = 7.5 Hz, 2H), 7.59 (t, J = 7.5 Hz, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.17-7.04 (m, 5H), 6.96 (s, 1H), 3.84 (s, 3H), 3.76 (s, 3H)。 Example 137: 3 ′-{N ′-[1- (3,4-dimethoxy-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 237)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.23 (s, 1H), 13.04 (s, 1H), 9.42 (s, 1H), 8.11 (s, 1H), 7.92 (dd, J = 7.5, 14.0 Hz, 2H) , 7.78 (t, J = 7.5 Hz, 2H), 7.59 (t, J = 7.5 Hz, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.17-7.04 (m, 5H), 6.96 (s, 1H), 3.84 (s, 3H), 3.76 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.16 (s, 1H), 13.04 (s, 1H), 9.48 (s, 1H), 8.11 (s, 1H), 7.94 (d, J = 7.5Hz, 2H), 7.80-7.77 (m, 2H), 7.60 (t, J = 7.5, Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.46-7.44 (m, 3H), 7.22 (s, 1H), 7.13 (t, J = 7.5 Hz, 1H), 7.06 (d, J = 7.5 Hz, 1H)。 Example 138: 3 ′-{N ′-[1- (3,5-difluoro-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 238)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.16 (s, 1H), 13.04 (s, 1H), 9.48 (s, 1H), 8.11 (s, 1H), 7.94 (d, J = 7.5Hz, 2H), 7.80 -7.77 (m, 2H), 7.60 (t, J = 7.5, Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.46-7.44 (m, 3H), 7.22 (s, 1H), 7.13 (t, J = 7.5 Hz, 1H), 7.06 (d, J = 7.5 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.11 (s, 1H), 13.07 (s, 1H), 9.34 (s, 1H), 8.14 (s, 1H), 7.97 (dd, J = 7.5, 16.0 Hz, 2H), 7.81 (d, J = 7.5 Hz, 1H), 7.60 (t, J = 7.5, Hz, 1H), 7.57-7.54 (m, 2H), 7.31 (d, J = 6.0 Hz, 2H), 6.98 (s, 1H), 6.91 (dd, J = 2.5, 9.5 Hz, 1H), 2.29 (s, 6H)。 Example 139: 5′-fluoro-3 ′-{N ′-[1- (4-fluoro-3,5-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole -3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 239)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.11 (s, 1H), 13.07 (s, 1H), 9.34 (s, 1H), 8.14 (s, 1H), 7.97 (dd, J = 7.5, 16.0 Hz, 2H) , 7.81 (d, J = 7.5 Hz, 1H), 7.60 (t, J = 7.5, Hz, 1H), 7.57-7.54 (m, 2H), 7.31 (d, J = 6.0 Hz, 2H), 6.98 (s , 1H), 6.91 (dd, J = 2.5, 9.5 Hz, 1H), 2.29 (s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.37 (s, 1H), 13.10 (s, 1H), 9.35 (s, 1H), 8.04 (dd, J = 2.0, 7.0 Hz, 1H), 7.98 (d, J = 7.5 Hz, 1H), 7.82-7.79 (m, 1H), 7.57-7.54 (m, 2H), 7.42 (t, J = 9.0 Hz, 1H), 7.30 (d, J = 6.5 Hz, 2H), 6.98 (s, 1H), 6.91 (dd, J = 2.5, 9.5 Hz, 1H), 2.29 (s, 6H)。 Example 140: 4,5′-difluoro-3 ′-{N ′-[1- (4-fluoro-3,5-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro -Indol-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 240)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.37 (s, 1H), 13.10 (s, 1H), 9.35 (s, 1H), 8.04 (dd, J = 2.0, 7.0 Hz, 1H), 7.98 (d, J = 7.5 Hz, 1H), 7.82-7.79 (m, 1H), 7.57-7.54 (m, 2H), 7.42 (t, J = 9.0 Hz, 1H), 7.30 (d, J = 6.5 Hz, 2H), 6.98 ( s, 1H), 6.91 (dd, J = 2.5, 9.5 Hz, 1H), 2.29 (s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.21 (s, 1H), 13.03 (s, 1H), 9.40 (s, 1H), 8.10 (s, 1H), 7.91 (dd, J = 8.0, 15.0 Hz, 2H), 7.77 (t, J = 7.5 Hz, 2H), 7.59 (t, J = 8.0 Hz, 1H), 7.52 (d, J = 7.5 Hz, 1H), 7.21 (s, 2H), 7.12 (t, J = 8.0 Hz, 1H), 7.04 (dd, J = 1.5, 7.5 Hz, 1H), 6.96 (s, 1H), 3.73 (s, 3H), 2.29 (s, 6H)。 Example 141: 2′-hydroxy-3 ′-{N ′-[1- (4-methoxy-3,5-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole -3-ylidene] -hydrazino} -biphenyl-3-carboxylic acid (Compound 241)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.21 (s, 1H), 13.03 (s, 1H), 9.40 (s, 1H), 8.10 (s, 1H), 7.91 (dd, J = 8.0, 15.0 Hz, 2H) , 7.77 (t, J = 7.5 Hz, 2H), 7.59 (t, J = 8.0 Hz, 1H), 7.52 (d, J = 7.5 Hz, 1H), 7.21 (s, 2H), 7.12 (t, J = 8.0 Hz, 1H), 7.04 (dd, J = 1.5, 7.5 Hz, 1H), 6.96 (s, 1H), 3.73 (s, 3H), 2.29 (s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.22 (s, 1H), 13.03 (s, 1H), 9.39 (s, 1H), 8.69 (s, 1H), 8.10 (s, 1H) , 7.93 (d, J = 8.0 Hz, 1H), 7.88 (d, J = 8.0Hz, 1H), 7.78-7.75 (m, 2H), 7.58 (t, J = 8.0 Hz, 1H), 7.50 (d, J = 8.5 Hz, 1H), 7.11 (t, J = 8.0 Hz, 1H), 7.06 (s, 2H), 7.03 (dd, J = 1.5, 7.5 Hz, 1H), 6.89 (s, 1H), 2.21 (s, 6H)。 Example 142: 2'-hydroxy-3 '-{N'-[1- (4-hydroxy-3,5-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole -3-ylidene] -hydrazino} -biphenyl-3-carboxylic acid (Compound 242)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.22 (s, 1H), 13.03 (s, 1H), 9.39 (s, 1H), 8.69 (s, 1H), 8.10 (s, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.88 (d, J = 8.0Hz, 1H), 7.78-7.75 (m, 2H), 7.58 (t, J = 8.0 Hz, 1H), 7.50 (d, J = 8.5 Hz, 1H) , 7.11 (t, J = 8.0 Hz, 1H), 7.06 (s, 2H), 7.03 (dd, J = 1.5, 7.5 Hz, 1H), 6.89 (s, 1H), 2.21 (s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.06 (s, 1H), 9.27 (s, 1H), 8.11 (s, 1H), 7.94 (d, J=7.8 Hz, 1H), 7.79 (d, J=7.8 Hz, 1H), 7.73 (m, 2H), 7.60 (t, J=7.8 Hz, 1H), 7.44 (s, 4H), 7.29 (t, J=7.6 Hz, 1H), 7.19 (t, J=7.6 Hz, 1H), 7.11 (t, J=7.8 Hz, 1H), 7.00 (d, J=7.6 Hz, 1H), 6.88 (d, J=7.6 Hz, 1H), 2.61 (m, 1H), 1.85 (m, 4H), 1.72 (m, 1H), 1.44 (m, 4H), 1.26 (m, 1H)。 Example 143: 3 ′-{N ′-[1- (4-cyclohexyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy-biphenyl-3 -Carboxylic acid (Compound 243)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.06 (s, 1H), 9.27 (s, 1H), 8.11 (s, 1H), 7.94 (d, J = 7.8 Hz, 1H), 7.79 (d, J = 7.8 Hz, 1H), 7.73 (m, 2H), 7.60 (t, J = 7.8 Hz, 1H), 7.44 (s, 4H), 7.29 (t, J = 7.6 Hz, 1H), 7.19 (t, J = 7.6 Hz, 1H), 7.11 (t, J = 7.8 Hz, 1H), 7.00 (d, J = 7.6 Hz, 1H), 6.88 (d, J = 7.6 Hz, 1H), 2.61 (m, 1H) , 1.85 (m, 4H), 1.72 (m, 1H), 1.44 (m, 4H), 1.26 (m, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.08 (s, 1H), 9.34 (s, 1H), 8.66 (ddd, J=4.9, 1.9, 0.9 Hz, 1H), 8.13 (t, J=1.6 Hz, 1H), 8.07 (ddd, J=7.6, 8.0, 1.9 Hz, 1H), 7.95 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.89 (dt, J=8.0, 1.0 Hz, 1H), 7.81 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.77-7.74 (m, 2H), 7.67 (d, J=7.8 Hz, 1H), 7.61 (t, J=7.7 Hz, 1H), 7.47 (ddd, J=7.6, 4.9, 1.0 Hz, 1H), 7.34 (td, J=7.8, 1.3 Hz, 1H), 7.25 (td, J=7.8, 0.9 Hz, 1H), 7.13 (t, J=7.8 Hz, 1H), 7.02 (dd, J=7.8, 1.6 Hz, 1H)。 Example 144: 2'-hydroxy-3 '-[N'-(2-oxo-1-pyridin-2-yl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid Acid (Compound 244)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.08 (s, 1H), 9.34 (s, 1H), 8.66 (ddd, J = 4.9, 1.9, 0.9 Hz, 1H), 8.13 (t, J = 1.6 Hz, 1H), 8.07 (ddd, J = 7.6, 8.0, 1.9 Hz, 1H), 7.95 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.89 (dt, J = 8.0, 1.0 Hz, 1H) , 7.81 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.77-7.74 (m, 2H), 7.67 (d, J = 7.8 Hz, 1H), 7.61 (t, J = 7.7 Hz, 1H), 7.47 (ddd, J = 7.6, 4.9, 1.0 Hz, 1H), 7.34 (td, J = 7.8, 1.3 Hz, 1H), 7.25 (td, J = 7.8, 0.9 Hz, 1H), 7.13 (t, J = 7.8 Hz, 1H), 7.02 (dd, J = 7.8, 1.6 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300 MHz, DMSO-d₆) δ 13.02 (s, 1H), 9.33 (s, 1H), 8.81 (s, 1H), 8.69 (s, 1H), 8.12 (t, J=1.6 Hz, 1H), 8.05 (ddd, J=8.2, 2.0, 1.6 Hz, 1H), 7.94 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.82-7.73 (m, 3H), 7.67 (m, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.32 (td, J=7.6, 1.4 Hz, 1H), 7.23 (td, J=7.6, 1.0 Hz, 1H), 7.12 (t, J=7.8 Hz, 1H), 7.02 (dd, J=7.8, 1.7 Hz, 1H), 6.94 (d, J=7.8 Hz, 1H)。 Example 145: 2′-hydroxy-3 ′-[N ′-(2-oxo-1-pyridin-3-yl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid Acid (Compound 245)

This compound was prepared as described in Scheme II. ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 13.02 (s, 1H), 9.33 (s, 1H), 8.81 (s, 1H), 8.69 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 8.05 (ddd, J = 8.2, 2.0, 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.82-7.73 (m, 3H), 7.67 (m, 1H) , 7.60 (t, J = 7.7 Hz, 1H), 7.32 (td, J = 7.6, 1.4 Hz, 1H), 7.23 (td, J = 7.6, 1.0 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 7.02 (dd, J = 7.8, 1.7 Hz, 1H), 6.94 (d, J = 7.8 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300 MHz, DMSO-d₆) δ 13.21 (s, 1H), 13.04 (s, 1H), 9.42 (s, 1H), 8.10 (s, 1H), 7.96-7.88 (m, 2H), 7.80-7.74 (m, 2H), 7.58 (t, J=7.7 Hz, 1H), 7.52 (d, J=7.9 Hz, 1H), 7.46 (s, 4H), 7.12 (t, J=7.8 Hz, 1H), 7.04 (d, J=7.8 Hz, 1H), 6.96 (s, 1H), 2.70 (q, J=7.6 Hz, 2H), 1.24 (t, J=7.6 Hz, 3H)。 Example 146: 3 ′-{N ′-[1- (4-ethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ′ -Hydroxy-biphenyl-3-carboxylic acid (Compound 246)

This compound was prepared as described in Scheme II. ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 13.21 (s, 1H), 13.04 (s, 1H), 9.42 (s, 1H), 8.10 (s, 1H), 7.96-7.88 (m, 2H), 7.80-7.74 (m, 2H), 7.58 (t, J = 7.7 Hz, 1H), 7.52 (d, J = 7.9 Hz, 1H), 7.46 (s, 4H), 7.12 (t, J = 7.8 Hz, 1H ), 7.04 (d, J = 7.8 Hz, 1H), 6.96 (s, 1H), 2.70 (q, J = 7.6 Hz, 2H), 1.24 (t, J = 7.6 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.36 (s, 1H), 13.05 (s, 1H), 9.50 (s, 1H), 8.12 (t, J=1.6 Hz, 1H), 7.95 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.80 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.67 (dd, J=7.8, 1.6 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.51 (d, J=9.5 Hz, 1H), 7.47 (s, 4H), 7.15 (t, J=7.8 Hz, 1H), 7.08 (dd, J=7.8, 1.6 Hz, 1H), 6.83 (s, 1H), 2.72 (q, J=7.6 Hz, 2H), 1.26 (t, J=7.6 Hz, 3H)。 Example 147: 3 ′-{N ′-[1- (4-ethyl-phenyl) -4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino } -2'-Hydroxy-biphenyl-3-carboxylic acid (Compound 247)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.36 (s, 1H), 13.05 (s, 1H), 9.50 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.95 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.80 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.67 (dd, J = 7.8, 1.6 Hz, 1H), 7.60 (t, J = 7.7 Hz , 1H), 7.51 (d, J = 9.5 Hz, 1H), 7.47 (s, 4H), 7.15 (t, J = 7.8 Hz, 1H), 7.08 (dd, J = 7.8, 1.6 Hz, 1H), 6.83 (s, 1H), 2.72 (q, J = 7.6 Hz, 2H), 1.26 (t, J = 7.6 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300 MHz, DMSO-d₆) δ 13.07 (s, 1H), 13.05 (s, 1H), 9.37 (s, 1H), 8.25 (s, 1H), 8.12 (s, 1H), 7.97-7.89 (m, 2H), 7.83-7.77 (m, 2H), 7.60 (t, J=7.8 Hz, 1H), 7.46 (s, 4H), 7.13 (t, J=7.8 Hz, 1H), 7.04 (d, J=7.8 Hz, 1H), 6.97 (d, J=8.6 Hz, 1H), 3.89 (s, 3H), 2.72 (q, J=7.5 Hz, 2H), 1.25 (t, J=7.5 Hz, 3H)。 Example 148: 3-[(3′-carboxy-2-hydroxy-biphenyl-3-yl) -hydrazono] -1- (3,5-dimethyl-phenyl) -2-oxo-2,3-dihydro-1 -H-indole-5-carboxylic acid methyl ester (Compound 248)

This compound was prepared as described in Scheme II. ¹ H NMR (300 MHz, DMSO-d ₆ ) δ 13.07 (s, 1H), 13.05 (s, 1H), 9.37 (s, 1H), 8.25 (s, 1H), 8.12 (s, 1H), 7.97- 7.89 (m, 2H), 7.83-7.77 (m, 2H), 7.60 (t, J = 7.8 Hz, 1H), 7.46 (s, 4H), 7.13 (t, J = 7.8 Hz, 1H), 7.04 (d , J = 7.8 Hz, 1H), 6.97 (d, J = 8.6 Hz, 1H), 3.89 (s, 3H), 2.72 (q, J = 7.5 Hz, 2H), 1.25 (t, J = 7.5 Hz, 3H ).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.19 (s, 1H), 13.05 (s, 1H), 9.46 (s, 1H), 8.12 (t, J=1.7 Hz, 1H), 7.95 (ddd, J=7.6, 1.7, 1.2 Hz, 1H), 7.93 (d, J=7.9 Hz, 1H), 7.80 (ddd, J=7.6, 1.7, 1.2 Hz, 1H), 7.78 (dd, J=7.8, 1.6 Hz, 1H), 7.70 (d, J=2.1 Hz, 1H), 7.61 (t, J=7.6 Hz, 1H), 7.61 (d, J=8.2 Hz, 1H), 7.56 (dq, J=7.9 , 0.7 Hz, 1H), 7.49 (dd, J=8.2, 2.1 Hz, 1H), 7.14 (t, J=7.8 Hz, 1H), 7.07 (dd, J=7.8, 1.6 Hz, 1H), 7.04 (m, 1H), 2.44 (s, 3H)。 Example 149: 3 ′-{N ′-[1- (3-chloro-4-methyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino } -2'-Hydroxy-biphenyl-3-carboxylic acid (Compound 249)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.19 (s, 1H), 13.05 (s, 1H), 9.46 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 7.95 (ddd, J = 7.6, 1.7, 1.2 Hz, 1H), 7.93 (d, J = 7.9 Hz, 1H), 7.80 (ddd, J = 7.6, 1.7, 1.2 Hz, 1H), 7.78 (dd, J = 7.8, 1.6 Hz , 1H), 7.70 (d, J = 2.1 Hz, 1H), 7.61 (t, J = 7.6 Hz, 1H), 7.61 (d, J = 8.2 Hz, 1H), 7.56 (dq, J = 7.9, 0.7 Hz , 1H), 7.49 (dd, J = 8.2, 2.1 Hz, 1H), 7.14 (t, J = 7.8 Hz, 1H), 7.07 (dd, J = 7.8, 1.6 Hz, 1H), 7.04 (m, 1H) , 2.44 (s, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.12 (s, 1H), 12.57 (s, 1H), 10.88 (s, 1H), 7.91 (d, J=7.9 Hz, 1H), 7.80 (d, J=8.4 Hz, 1H), 7.68 (s, 1H), 7.54 (dq, J=7.9, 0.8 Hz, 1H), 7.24 (dd, J=8.4, 1.8 Hz, 1H), 7.18 (s, 1H), 7.17-7.15 (m, 3 H), 6.97 (m, 1H), 2.37 (s, 6H)。 Example 150: 5- (4- {N '-[1- (3,5-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino } -3-Hydroxy-benzylidene) -thiazolidine-2,4-dione (Compound 250)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.12 (s, 1H), 12.57 (s, 1H), 10.88 (s, 1H), 7.91 (d, J = 7.9 Hz, 1H), 7.80 (d, J = 8.4 Hz, 1H), 7.68 (s, 1H), 7.54 (dq, J = 7.9, 0.8 Hz, 1H), 7.24 (dd, J = 8.4, 1.8 Hz, 1H), 7.18 (s, 1H), 7.17-7.15 (m, 3 H), 6.97 (m, 1H), 2.37 (s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.02 (s, 1H), 9.26 (s, 1H), 8.12 (t, J=1.7 Hz, 1H), 7.95 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.79 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.69 (dd, J=7.8, 1.6 Hz, 1H), 7.65 (dd, J=7.6, 1.2 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.35 (td, J=7.6, 1.2 Hz, 1H), 7.24 (d, J=7.6 Hz, 1H), 7.14 (td, J=7.6, 0.8 Hz, 1H), 7.10 (t, J=7.8 Hz, 1H), 6.98 (dd, J=7.8, 1.6 Hz, 1H), 3.90 (t, J=7.0 Hz, 2H), 2.39 (m, 2H), 1.88 (m, 2H)。 Example 151: 2′-hydroxy-3 ′-(N ′-{2-oxo-1- [4- (4,4,4-trifluoro-butyl) -phenyl] -1,2-dihydro-indole- 3-Ilidene} -hydrazino) -biphenyl-3-carboxylic acid (Compound 251)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.02 (s, 1H), 9.26 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 7.95 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.69 (dd, J = 7.8, 1.6 Hz, 1H), 7.65 (dd, J = 7.6, 1.2 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.35 (td, J = 7.6, 1.2 Hz, 1H), 7.24 (d, J = 7.6 Hz, 1H), 7.14 (td, J = 7.6, 0.8 Hz, 1H) , 7.10 (t, J = 7.8 Hz, 1H), 6.98 (dd, J = 7.8, 1.6 Hz, 1H), 3.90 (t, J = 7.0 Hz, 2H), 2.39 (m, 2H), 1.88 (m, 2H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.37 (s, 1H), 13.06 (s, 1H), 9.49 (s, 1H), 8.12 (t, J=1.7 Hz, 1H), 7.95 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.80 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.67 (dd, J=7.8, 1.6 Hz, 1H), 7.61 (t, J=7.7 Hz, 1H), 7.50 (d, J=9.5 Hz, 1H), 7.18 (m, 1H), 7.16 (m, 2H), 7.15 (t, J=7.8 Hz, 1H), 7.08 (dd, J=7.8, 1.6 Hz, 1H), 6.83 (s, 1H), 2.37 (s, 6H)。 Example 152: 3 '-{N'-[1- (3,5-dimethyl-phenyl) -4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -Hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 252)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.37 (s, 1H), 13.06 (s, 1H), 9.49 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 7.95 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.80 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.67 (dd, J = 7.8, 1.6 Hz, 1H), 7.61 (t, J = 7.7 Hz , 1H), 7.50 (d, J = 9.5 Hz, 1H), 7.18 (m, 1H), 7.16 (m, 2H), 7.15 (t, J = 7.8 Hz, 1H), 7.08 (dd, J = 7.8, 1.6 Hz, 1H), 6.83 (s, 1H), 2.37 (s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.23 (s, 1H), 13.05 (s, 1H), 9.44 (s, 1H), 8.12 (t, J=1.7 Hz, 1H), 7.95 (ddd, J=7.7, 1.7, 1.1 Hz, 1H), 7.93 (d, J=7.8 Hz, 1H), 7.80 (ddd, J=7.7, 1.7, 1.1 Hz, 1H), 7.78 (dd, J=7.8, 1.6 Hz, 1H), 7.65 (d, J=8.7 Hz, 2H), 7.61 (t, J=7.7 Hz, 1H), 7.55 (dq, J=7.8, 0.7 Hz, 1H), 7.50 (d, J=8.7 Hz, 2H), 7.14 (t, J=7.8 Hz, 1H), 7.06 (dd, J=7.8, 1.6 Hz, 1H), 7.01 (q, J=0.8 Hz, 1H), 1.36 (s, 9H)。 Example 153: 3 ′-{N ′-[1- (4-tert-butyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 253)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.23 (s, 1H), 13.05 (s, 1H), 9.44 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 7.95 (ddd, J = 7.7, 1.7, 1.1 Hz, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.80 (ddd, J = 7.7, 1.7, 1.1 Hz, 1H), 7.78 (dd, J = 7.8, 1.6 Hz , 1H), 7.65 (d, J = 8.7 Hz, 2H), 7.61 (t, J = 7.7 Hz, 1H), 7.55 (dq, J = 7.8, 0.7 Hz, 1H), 7.50 (d, J = 8.7 Hz , 2H), 7.14 (t, J = 7.8 Hz, 1H), 7.06 (dd, J = 7.8, 1.6 Hz, 1H), 7.01 (q, J = 0.8 Hz, 1H), 1.36 (s, 9H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, CD₃OD) δ 8.09 (d, J=8.2 Hz, 2H), 7.89 (d, J=7.9 Hz, 1H), 7.81 (dd, J=7.9, 1.6 Hz, 1H), 7.63 (d, J=8.2 Hz, 2H), 7.47 (d, J=7.9 Hz, 1H), 7.38 (d, J=8.0 Hz, 1H), 7.26 (d, J=1.8 Hz, 1H), 7.19 (dd, J=8.0, 1.8 Hz, 1H), 7.10 (t, J=7.9 Hz, 1H), 7.04 (dd, J=7.9, 1.6 Hz, 1H), 6.99 (s, 1H), 2.38 (s, 3H), 2.37 (s, 3H)。 Example 154: 3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-4-carboxylic acid (Compound 254)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, CD ₃ OD) δ 8.09 (d, J = 8.2 Hz, 2H), 7.89 (d, J = 7.9 Hz, 1H), 7.81 (dd, J = 7.9, 1.6 Hz, 1H), 7.63 (d, J = 8.2 Hz, 2H), 7.47 (d, J = 7.9 Hz, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.26 (d, J = 1.8 Hz, 1H), 7.19 (dd , J = 8.0, 1.8 Hz, 1H), 7.10 (t, J = 7.9 Hz, 1H), 7.04 (dd, J = 7.9, 1.6 Hz, 1H), 6.99 (s, 1H), 2.38 (s, 3H) , 2.37 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO-d₆) δ 13.08 (s, 1H), 13.04 (s, 1H), 9.33 (s, 1H), 8.12 (m, 1H), 7.94 (d, J=7.7 Hz, 1H), 7.79 (m, 1H), 7.74 (d, J=7.7 Hz, 1H), 7.67 (d, J=8.0 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.37 (d, J=8.0 Hz, 1H), 7.37 (d, J=8.0 Hz, 1H), 7.31 (d, J=1.8 Hz, 1H), 7.24 (dd, J=8.0, 1.8 Hz, 1H), 7.12 (t, J=7.9 Hz, 1H), 7.03 (m, 1H), 6.91 (m, 1H), 2.32 (s, 3H), 2.31 (s, 3H)。 Example 155: 3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -2-oxo-6-bromo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ′ -Hydroxy-biphenyl-3-carboxylic acid (Compound 255)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO-d ₆ ) δ 13.08 (s, 1H), 13.04 (s, 1H), 9.33 (s, 1H), 8.12 (m, 1H), 7.94 (d, J = 7.7 Hz, 1H ), 7.79 (m, 1H), 7.74 (d, J = 7.7 Hz, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.31 (d, J = 1.8 Hz, 1H), 7.24 (dd, J = 8.0, 1.8 Hz, 1H), 7.12 (t, J = 7.9 Hz, 1H), 7.03 (m, 1H), 6.91 (m, 1H), 2.32 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO-d₆) δ 13.27 (s, 1H), 13.22 (s, 1H), 9.59 (s, 1H), 7.97-7.91 (m, 2H), 7.81 (dd, J=7.7, 1.5 Hz, 1H), 7.54 (d, J=7.6 Hz, 1H), 7.51-7.47 (m, 2H), 7.39 (d, J=8.0 Hz, 1H), 7.33 (d, J=1.8 Hz, 1H), 7.27 (dd, J=8.0, 1.8 Hz, 1H), 7.15 (t, J=7.7 Hz, 1H), 7.10 (dd, J=7.7, 1.5 Hz, 1H), 6.96 (s, 1H), 2.32 (s, 3H), 2.31 (s, 3H)。 Example 156: 3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 3-Fluoro-2'-hydroxy-biphenyl-4-carboxylic acid (Compound 256)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO-d ₆ ) δ 13.27 (s, 1H), 13.22 (s, 1H), 9.59 (s, 1H), 7.97-7.91 (m, 2H), 7.81 (dd, J = 7.7, 1.5 Hz, 1H), 7.54 (d, J = 7.6 Hz, 1H), 7.51-7.47 (m, 2H), 7.39 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 1.8 Hz, 1H) , 7.27 (dd, J = 8.0, 1.8 Hz, 1H), 7.15 (t, J = 7.7 Hz, 1H), 7.10 (dd, J = 7.7, 1.5 Hz, 1H), 6.96 (s, 1H), 2.32 ( s, 3H), 2.31 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300MHz, CD₃OD) δ 8.24 (s, 2H), 8.11 (s, 2H), 7.99-7.92 (m, 2H), 7.81 (m, 1H), 7.65 (m, 1H), 7.56-7.45 (m, 2H), 7.18 (s, 1H), 7.11-7.02 (m, 2H)。 Example 157: 3 ′-{N ′-[1- (3,5-bis-trifluoromethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -Hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 257)

This compound was prepared as described in Scheme II. ¹ H NMR (300MHz, CD ₃ OD) δ 8.24 (s, 2H), 8.11 (s, 2H), 7.99-7.92 (m, 2H), 7.81 (m, 1H), 7.65 (m, 1H), 7.56- 7.45 (m, 2H), 7.18 (s, 1H), 7.11-7.02 (m, 2H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO-d₆) δ 13.17 (s, 1H), 13.05 (s, 1H), 9.47 (s, 1H), 8.12 (t, J=1.7 ,Hz, 1H), 7.97-7.93 (m, 3H), 7.91 (d, J=8.5 Hz, 1H), 7.81-7.77 (m, 2H), 7.64 (dd, J=8.5, 2.4 Hz, 1H), 7.61 (t, J=7.7 Hz, 1H), 7.57 (d, J=8.5 Hz, 1H), 7.18 (s, 1H), 7.14 (t, J=7.7 Hz, 1H), 7.07 (dd, J=7.7, 1.6 Hz, 1H)。 Example 158: 3 ′-{N ′-[1- (3,4-dichloro-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 258)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO-d ₆ ) δ 13.17 (s, 1H), 13.05 (s, 1H), 9.47 (s, 1H), 8.12 (t, J = 1.7, Hz, 1H), 7.97-7.93 ( m, 3H), 7.91 (d, J = 8.5 Hz, 1H), 7.81-7.77 (m, 2H), 7.64 (dd, J = 8.5, 2.4 Hz, 1H), 7.61 (t, J = 7.7 Hz, 1H ), 7.57 (d, J = 8.5 Hz, 1H), 7.18 (s, 1H), 7.14 (t, J = 7.7 Hz, 1H), 7.07 (dd, J = 7.7, 1.6 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300MHz, CD₃OD) δ 8.13 (s, 1H), 7.97 (d, J=7.7 Hz, 1H), 7.91 (d, J=7.7 Hz, 1H), 7.79 (m, 1H), 7.66 (d, J=7.7 Hz, 1H), 7.62-7.59 (m, 3H), 7.54-7.47 (m, 2H), 7.16-7.02 (m, 3H)。 Example 159: 3 ′-{N ′-[1- (3,5-dichloro-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 259)

This compound was prepared as described in Scheme II. ¹ H NMR (300MHz, CD ₃ OD) δ 8.13 (s, 1H), 7.97 (d, J = 7.7 Hz, 1H), 7.91 (d, J = 7.7 Hz, 1H), 7.79 (m, 1H), 7.66 (d, J = 7.7 Hz, 1H), 7.62-7.59 (m, 3H), 7.54-7.47 (m, 2H), 7.16-7.02 (m, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500MHz, DMSO-d₆) δ 13.14 (s, 1H), 12.45 (s, 1H), 10.61 (s, 1H), 7.90 (d, J=8.0 Hz, 1H), 7.75 (d, J=8.1 Hz, 1H), 7.55-7.51 (m, 2H), 7.18 (s, 1H), 7.16 (s, 2H), 7.12-7.09 (m, 2H), 6.98 (s, 1H), 2.37 (s, 6H), 2.08 (d, J=1.0 Hz, 3H)。 Example 160: 3- (4- {N '-[1- (3,5-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino } -3-Hydroxy-phenyl) -2-methyl-acrylic acid (Compound 260)

This compound was prepared as described in Scheme V. ¹ H NMR (500MHz, DMSO-d ₆ ) δ 13.14 (s, 1H), 12.45 (s, 1H), 10.61 (s, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.75 (d, J = 8.1 Hz, 1H), 7.55-7.51 (m, 2H), 7.18 (s, 1H), 7.16 (s, 2H), 7.12-7.09 (m, 2H), 6.98 (s, 1H), 2.37 (s, 6H), 2.08 (d, J = 1.0 Hz, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (300MHz, DMSO-d₆) δ 13.13 (s, 1H), 12.45 (s, 1H), 10.61 (s, 1H), 7.90 (m, 1H), 7.75 (m, 1H), 7.56-7.50 (m, 2H), 7.39 (m, 1H), 7.33 (s, 1H), 7.26 (m, 1H), 7.13-7.08 (m, ,2H), 6.96 (s, 1H), 2.32 (s, 3H), 2.31 (s, 3H), 2.08 (s, 3H)。 Example 161: 3- (4- {N '-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino } -3-Hydroxy-phenyl) -2-methyl-acrylic acid (Compound 261)

This compound was prepared as described in Scheme V. ¹ H NMR (300MHz, DMSO-d ₆ ) δ 13.13 (s, 1H), 12.45 (s, 1H), 10.61 (s, 1H), 7.90 (m, 1H), 7.75 (m, 1H), 7.56-7.50 (m, 2H), 7.39 (m, 1H), 7.33 (s, 1H), 7.26 (m, 1H), 7.13-7.08 (m,, 2H), 6.96 (s, 1H), 2.32 (s, 3H) , 2.31 (s, 3H), 2.08 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO-d₆) δ 13.16 (s, 1H), 10.91 (s, 1H), 8.15 (t, J=1.4 Hz, 1H), 7.95 (ddd, J = 7.8, 1.4, 1.2 Hz, 1H), 7.79 (ddd, J =7.8, 1.4, 1.2 Hz, 1H), 7.72 (dd, J =7.9, 1.5 Hz, 1H), 7.63 (dd, J =7.6, 1.2 Hz, 1H), 7.58 (t, J =7.8 Hz, 1H), 7.56-7.46 (m, 4H), 7.41 (m, 1H), 7.26 (dd, J =7.6, 1.2 Hz, 1H), 7.18 (t, J =7.6 Hz, 1H), 7.11 (t, J =7.9 Hz, 1H), 6.99 (dd, J =7.9, 1.5 Hz, 1H)。 Example 162: 2′-hydroxy-3 ′-[N ′-(2-oxo-7-phenyl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid (Compound 262 )

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO-d ₆ ) δ 13.16 (s, 1H), 10.91 (s, 1H), 8.15 (t, J = 1.4 Hz, 1H), 7.95 (ddd, J = 7.8, 1.4, 1.2 Hz , 1H), 7.79 (ddd, J = 7.8, 1.4, 1.2 Hz, 1H), 7.72 (dd, J = 7.9, 1.5 Hz, 1H), 7.63 (dd, J = 7.6, 1.2 Hz, 1H), 7.58 ( t, J = 7.8 Hz, 1H), 7.56-7.46 (m, 4H), 7.41 (m, 1H), 7.26 (dd, J = 7.6, 1.2 Hz, 1H), 7.18 (t, J = 7.6 Hz, 1H ), 7.11 (t, J = 7.9 Hz, 1H), 6.99 (dd, J = 7.9, 1.5 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO-d₆) δ 13.27 (s, 1H), 13.02 (s, 1H), 9.39 (s, 1H), 8.12 (s, 1H), 7.95 (m, 1H), 7.80 (m, 1H), 7.65-7.58 (m, 2H), 7.42-7.24 (m, 4H), 7.22-7.11 (m, 2H), 7.04 (m, 1H), 6.89 (m, 1H), 2.32 (s, 3H), 2.30 (s, 3H)。 Example 163: 3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethoxy-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 263)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO-d ₆ ) δ 13.27 (s, 1H), 13.02 (s, 1H), 9.39 (s, 1H), 8.12 (s, 1H), 7.95 (m, 1H), 7.80 (m , 1H), 7.65-7.58 (m, 2H), 7.42-7.24 (m, 4H), 7.22-7.11 (m, 2H), 7.04 (m, 1H), 6.89 (m, 1H), 2.32 (s, 3H ), 2.30 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500MHz, DMSO) δ 13.07 (s, 1H), 13.04 (s, 1H), 9.33 (s, 1H), 8.12 (t, J=1.6 Hz, 1H), 7.94 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.80 (d, J=8.2 Hz, 1H), 7.79 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.74 (dd, J=7.8, 1.6 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.37 (d, J=8.1 Hz, 1H), 7.32 (d, J=2.0 Hz, 1H), 7.25 (dd, J=8.1, 2.0 Hz, 1H), 7.12 (t, J=7.8 Hz, 1H), 7.09 (dd, J=8.2, 2.1 Hz, 1H), 7.02 (dd, J=7.8, 1.6 Hz, 1H), 6.78 (tt, J=52.1, 3.1 Hz, 1H), 6.63 (d, J=2.1 Hz, 1H), 2.32 (s, 3H), 2.30 (s, 3H)。 Example 164: 3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -2-oxo-6- (1,1,2,2-tetrafluoro-ethoxy) -1,2-dihydro -Indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 264)

This compound was prepared as described in Scheme II. ¹ H NMR (500MHz, DMSO) δ 13.07 (s, 1H), 13.04 (s, 1H), 9.33 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.80 (d, J = 8.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.74 (dd, J = 7.8, 1.6 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.37 (d, J = 8.1 Hz, 1H), 7.32 (d, J = 2.0 Hz, 1H), 7.25 (dd, J = 8.1, 2.0 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 7.09 (dd, J = 8.2, 2.1 Hz, 1H), 7.02 (dd, J = 7.8, 1.6 Hz, 1H), 6.78 (tt, J = 52.1, 3.1 Hz , 1H), 6.63 (d, J = 2.1 Hz, 1H), 2.32 (s, 3H), 2.30 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.04 (s, 2H), 9.26 (s, 1H), 8.12 (t, J=1.6 Hz, 1H), 7.94 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.78 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.72 (dd, J=7.9, 1.6 Hz, 1H), 7.59 (t, J=7.7 Hz, 1H), 7.55 (s, 1H), 7.34 (d, J=8.1 Hz, 1H), 7.28 (d, J=2.0 Hz, 1H), 7.22 (dd, J=8.1, 2.0 Hz, 1H), 7.11 (t, J=7.9, Hz, 1H), 7.09 (m, 1H), 6.99 (dd, J=7.9, 1.6 Hz, 1H), 6.76 (d, J=8.0 Hz, 1H), 2.37 (s, 3H), 2.31 (s, 3H), 2.30 (s, 3H)。 Example 165: 3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -5-methyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ′ -Hydroxy-biphenyl-3-carboxylic acid (Compound 265)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.04 (s, 2H), 9.26 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.78 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.72 (dd, J = 7.9, 1.6 Hz, 1H), 7.59 (t, J = 7.7 Hz, 1H), 7.55 (s , 1H), 7.34 (d, J = 8.1 Hz, 1H), 7.28 (d, J = 2.0 Hz, 1H), 7.22 (dd, J = 8.1, 2.0 Hz, 1H), 7.11 (t, J = 7.9, Hz, 1H), 7.09 (m, 1H), 6.99 (dd, J = 7.9, 1.6 Hz, 1H), 6.76 (d, J = 8.0 Hz, 1H), 2.37 (s, 3H), 2.31 (s, 3H ), 2.30 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.03 (s, 2H), 9.26 (s, 1H), 8.11 (t, J=1.6 Hz, 1H), 7.94 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.79 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.72 (dd, J=7.9, 1.6 Hz, 1H), 7.59 (t, J=7.7 Hz, 1H), 7.56 (s, 1H), 7.46 (d, J=8.6 Hz, 2H), 7.43 (d, J=8.6 Hz, 2H), 7.11(t, J=7.9 Hz, 1H), 7.10 (m, 1H), 6.99 (dd, J=7.9, 1.6 Hz, 1H), 6.79 (d, J=8.2 Hz, 1H), 3.00 (sept, J=6.9 Hz, 1H), 2.37 (s, 3H), 1.26 (d, J=6.9 Hz, 6H)。 Example 166: 3 ′-{N ′-[1- (4-Isopropyl-phenyl) -5-methyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy -Biphenyl-3-carboxylic acid (Compound 266)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.03 (s, 2H), 9.26 (s, 1H), 8.11 (t, J = 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.79 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.72 (dd, J = 7.9, 1.6 Hz, 1H), 7.59 (t, J = 7.7 Hz, 1H), 7.56 (s , 1H), 7.46 (d, J = 8.6 Hz, 2H), 7.43 (d, J = 8.6 Hz, 2H), 7.11 (t, J = 7.9 Hz, 1H), 7.10 (m, 1H), 6.99 (dd , J = 7.9, 1.6 Hz, 1H), 6.79 (d, J = 8.2 Hz, 1H), 3.00 (sept, J = 6.9 Hz, 1H), 2.37 (s, 3H), 1.26 (d, J = 6.9 Hz , 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.10 (s, 1H), 13.05 (s, 1H), 9.30 (s, 1H), 8.13 (t, J=1.6 Hz, 1H), 7.95 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.81 (d, J=7.8 Hz, 1H), 7.80 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.75 (dd, J=7.9, 1.5 Hz, 1H), 7.62-7.57 (m, 3H), 7.48 (dd, J=7.8, 1.8 Hz, 1H), 7.47-7.42 (m, 2H), 7.39-7.34 (m, 3H), 7.30 (dd, J=7.8, 2.2 Hz, 1H), 7.13 (t, J=7.9 Hz, 1H), 7.02-7.00 (m, 2H), 2.32 (s, 3H), 2.31 (s, 3H)。 Example 167: 3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -6-phenyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ′ -Hydroxy-biphenyl-3-carboxylic acid (Compound 267)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.10 (s, 1H), 13.05 (s, 1H), 9.30 (s, 1H), 8.13 (t, J = 1.6 Hz, 1H), 7.95 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.80 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.75 (dd, J = 7.9, 1.5 Hz , 1H), 7.62-7.57 (m, 3H), 7.48 (dd, J = 7.8, 1.8 Hz, 1H), 7.47-7.42 (m, 2H), 7.39-7.34 (m, 3H), 7.30 (dd, J = 7.8, 2.2 Hz, 1H), 7.13 (t, J = 7.9 Hz, 1H), 7.02-7.00 (m, 2H), 2.32 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.19 (s, 1H), 13.05 (s, 1H), 9.47 (s, 1H), 8.12 (t, J=1.7 Hz, 1H), 8.03 (s, 1H), 7.97-7.93 (m, 3H), 7.93-7.86 (m, 2H), 7.80 (dd, J=7.8, 1.6 Hz, 1H), 7.80 (ddd, J=7.8, 1.7, 1.2 Hz, 1H), 7.61 (t, J=7.8 Hz, 1H), 7.58 (dq, J=7.8, 0.8 Hz, 1H), 7.15 (t, J=7.8 Hz, 1H), 7.10 (d, J=0.7 Hz, 1H), 7.08 (dd, J=7.8, 1.6 Hz, 1H)。 Example 168: 3 ′-{N ′-[1- (3-trifluoromethyl-phenyl) -6-trifluoromethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 268)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.19 (s, 1H), 13.05 (s, 1H), 9.47 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 8.03 (s, 1H), 7.97-7.93 (m, 3H), 7.93-7.86 (m, 2H), 7.80 (dd, J = 7.8, 1.6 Hz, 1H), 7.80 (ddd, J = 7.8, 1.7, 1.2 Hz, 1H) , 7.61 (t, J = 7.8 Hz, 1H), 7.58 (dq, J = 7.8, 0.8 Hz, 1H), 7.15 (t, J = 7.8 Hz, 1H), 7.10 (d, J = 0.7 Hz, 1H) , 7.08 (dd, J = 7.8, 1.6 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.10 (s, 1H), 13.05 (s, 1H), 9.40 (s, 1H), 8.12 (t, J=1.6 Hz, 1H), 7.95 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.82 (dd, J=7.8, 1.6 Hz, 1H), 7.80 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.74 (m, 1H), 7.73 (d, J=9.0 Hz, 2H), 7.62 (dq, J=9.0, 0.9 Hz, 2H), 7.60 (t, J=7.7 Hz, 1H), 7.28 (ddq, J=8.6, 2.1, 0.9 Hz, 1H), 7.13 (t, J=7.8 Hz, 1H), 7.05 (dd, J=7.8, 1.6 Hz, 1H), 7.02 (d, J=8.6 Hz, 1H)。 Example 169: 3 ′-{N ′-[1- (4-trifluoromethoxy-phenyl) -5-trifluoromethoxy-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 269)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.10 (s, 1H), 13.05 (s, 1H), 9.40 (s, 1H), 8.12 (t, J = 1.6 Hz, 1H), 7.95 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.82 (dd, J = 7.8, 1.6 Hz, 1H), 7.80 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.74 (m, 1H), 7.73 (d, J = 9.0 Hz, 2H), 7.62 (dq, J = 9.0, 0.9 Hz, 2H), 7.60 (t, J = 7.7 Hz, 1H), 7.28 (ddq, J = 8.6, 2.1, 0.9 Hz, 1H), 7.13 (t, J = 7.8 Hz, 1H), 7.05 (dd, J = 7.8, 1.6 Hz, 1H), 7.02 (d, J = 8.6 Hz, 1H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.24 (s, 1H), 13.05 (s, 1H), 9.43 (s, 1H), 8.12 (t, J=1.7 Hz, 1H), 7.95 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.93 (d, J=7.8 Hz, 1H), 7.80 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.78 (dd, J=7.7, 1.7 Hz, 1H), 7.61 (t, J=7.7 Hz, 1H), 7.54 (dq, J=7.8, 0.8 Hz, 1H), 7.18-7.16 (m, 3H), 7.14 (t, J=7.7 Hz, 1H), 7.07 (dd, J=7.7, 1.7 Hz, 1H), 6.98 (m, 1H), 2.37(s, 3H), 2.37 (s, 3H)。 Example 170: 3 ′-{N ′-[1- (3,5-dimethyl-phenyl) -6-trifluoromethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 270)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.24 (s, 1H), 13.05 (s, 1H), 9.43 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 7.95 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.80 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.78 (dd, J = 7.7, 1.7 Hz , 1H), 7.61 (t, J = 7.7 Hz, 1H), 7.54 (dq, J = 7.8, 0.8 Hz, 1H), 7.18-7.16 (m, 3H), 7.14 (t, J = 7.7 Hz, 1H) , 7.07 (dd, J = 7.7, 1.7 Hz, 1H), 6.98 (m, 1H), 2.37 (s, 3H), 2.37 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.04 (s, 1H), 13.03 (s, 1H), 9.23 (s, 1H), 8.12 (t, J=1.7 Hz, 1H), 7.95 (m, 1H), 7.94 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.89-7.83 (m, 3H), 7.79 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.61 (dd, J=8.1, 1.4 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.12 (t, J=7.8 Hz, 1H), 6.98 (dd, J=7.8, 1.6 Hz, 1H), 6.87 (s, 1H), 6.57 (s, 1H), 2.65 (s, 3H), 2.29 (s, 3H)。 Example 171: 3 ′-{N ′-[1- (3-trifluoromethyl-phenyl) -4,6-dimethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 271)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.04 (s, 1H), 13.03 (s, 1H), 9.23 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 7.95 (m, 1H), 7.94 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.89-7.83 (m, 3H), 7.79 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.61 (dd, J = 8.1, 1.4 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 6.98 (dd, J = 7.8, 1.6 Hz, 1H), 6.87 (s, 1H), 6.57 (s, 1H), 2.65 (s, 3H), 2.29 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.04 (s, 1H), 12.91 (s, 1H), 9.25 (s, 1H), 8.12 (t, J=1.7 Hz, 1H), 7.95 (m, 1H), 7.94 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.90-7.84 (m, 3H), 7.79 (ddd, J=7.7, 1.7, 1.2 Hz, 1H), 7.71 (dd, J=8.0, 1.4 Hz, 1H), 7.60 (t, J=7.7 Hz, 1H), 7.55 (s, 1H), 7.11 (t, J=7.8 Hz, 1H), 6.99 (dd, J=7.8, 1.6 Hz, 1H), 6.76 (s, 1H), 2.29 (s, 3H), 2.25 (s, 3H)。 Example 172: 3 '-{N'-[1- (3-trifluoromethyl-phenyl) -5,6-dimethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid (Compound 272)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.04 (s, 1H), 12.91 (s, 1H), 9.25 (s, 1H), 8.12 (t, J = 1.7 Hz, 1H), 7.95 (m, 1H), 7.94 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.90-7.84 (m, 3H), 7.79 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), 7.71 (dd, J = 8.0, 1.4 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.55 (s, 1H), 7.11 (t, J = 7.8 Hz, 1H), 6.99 (dd, J = 7.8, 1.6 Hz, 1H), 6.76 (s, 1H), 2.29 (s, 3H), 2.25 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.39 (s, 1H), 13.11 (s, 1H), 9.69 (s, 1H), 8.02 (d, J=8.0 Hz, 1H), 8.02 (dd, J=7.0, 2.5 Hz, 1H), 7.81 (ddd, J=8.5, 4.6, 2.5 Hz, 1H), 7.76 (d, J=2.6 Hz, 1H), 7.54 (dq, J=8.0, 0.7 Hz, 1H), 7.43 (dd, J=10.7, 8.5 Hz, 1H), 7.17 (s, 1H), 7.16 (s, 2H), 7.08 (d, J=2.6 Hz, 1H), 6.97 (s, 1H), 2.37 (s, 6H)。 Example 173: 3 ′-{N ′-[1- (3,5-dimethyl-phenyl) -6-trifluoromethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2′-Hydroxy-5′-chloro-4-fluoro-biphenyl-3-carboxylic acid (Compound 273)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.39 (s, 1H), 13.11 (s, 1H), 9.69 (s, 1H), 8.02 (d, J = 8.0 Hz, 1H), 8.02 (dd, J = 7.0, 2.5 Hz, 1H), 7.81 (ddd, J = 8.5, 4.6, 2.5 Hz, 1H), 7.76 (d, J = 2.6 Hz, 1H), 7.54 (dq, J = 8.0, 0.7 Hz, 1H ), 7.43 (dd, J = 10.7, 8.5 Hz, 1H), 7.17 (s, 1H), 7.16 (s, 2H), 7.08 (d, J = 2.6 Hz, 1H), 6.97 (s, 1H), 2.37 (s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.35 (s, 1H), 13.23 (s, 1H), 9.44 (s, 1H), 8.01 (dd, J=7.2, 2.4 Hz, 1H), 7.92 (d, J=8.0 Hz, 1H), 7.79 (ddd, J=8.6, 4.6, 2.4 Hz, 1H), 7.79 (dd, J=7.8, 1.5 Hz, 1H), 7.54 (dq, J=8.0, 0.8 Hz, 1H), 7.42 (dd, J=10.7, 8.6 Hz, 1H), 7.17 (s, 1H), 7.16 (s, 2H), 7.13 (t, J=7.8 Hz, 1H), 7.05 (dd, J=7.8, 1.5 Hz, 1H), 6.98 (s, 1H), 2.37 (s, 6H)。 Example 174: 3 ′-{N ′-[1- (3,5-dimethyl-phenyl) -6-trifluoromethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-4-fluoro-biphenyl-3-carboxylic acid (compound 274)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.35 (s, 1H), 13.23 (s, 1H), 9.44 (s, 1H), 8.01 (dd, J = 7.2, 2.4 Hz, 1H), 7.92 ( d, J = 8.0 Hz, 1H), 7.79 (ddd, J = 8.6, 4.6, 2.4 Hz, 1H), 7.79 (dd, J = 7.8, 1.5 Hz, 1H), 7.54 (dq, J = 8.0, 0.8 Hz , 1H), 7.42 (dd, J = 10.7, 8.6 Hz, 1H), 7.17 (s, 1H), 7.16 (s, 2H), 7.13 (t, J = 7.8 Hz, 1H), 7.05 (dd, J = 7.8, 1.5 Hz, 1H), 6.98 (s, 1H), 2.37 (s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.06 (s, 1H), 13.00 (s, 1H), 9.33 (s, 1H), 8.12 (s, 1H), 7.94 (m, 1H), 7.81-7.70 (m, 3H), 7.60 (t, J=7.9 Hz, 1H), 7.37 (d, J=8.4 Hz, 1H), 7.31 (m, 1H), 7.27-7.21 (m, 2H), 7.12 (t, J=7.8 Hz, 1H), 7.02 (d, J=7.8, 1H), 6.79 (m, 1H), 2.31 (s, 3H), 2.31 (s, 3H)。 Example 175: 3 ′-{N ′-[6-chloro-1- (3,4-dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ′ -Hydroxy-biphenyl-3-carboxylic acid (Compound 275)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.06 (s, 1H), 13.00 (s, 1H), 9.33 (s, 1H), 8.12 (s, 1H), 7.94 (m, 1H), 7.81- 7.70 (m, 3H), 7.60 (t, J = 7.9 Hz, 1H), 7.37 (d, J = 8.4 Hz, 1H), 7.31 (m, 1H), 7.27-7.21 (m, 2H), 7.12 (t , J = 7.8 Hz, 1H), 7.02 (d, J = 7.8, 1H), 6.79 (m, 1H), 2.31 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300 MHz, アセトン-d₆) δ 8.19 (t, J=1.5 Hz, 1H), 8.03 (m, 1H), 7.83 (dd, J=7.8, 1.6 Hz, 1H), 7.77 (m, 1H), 7.59 (t, J=7.6 Hz, 1H), 7.53 (dd, J=8.3, 2.6 Hz, 1H), 7.47 (d, J=8.8 Hz, 2H), 7.43 (d, J=8.8 Hz, 2H), 7.13 (t, J=7.8 Hz, 1H), 7.06-7.02 (m, 2H), 6.92 (dd, J=8.8, 4.3 Hz, 1H), 2.69 (dd, J=7.9, 7.3 Hz, 2H), 1.71 (m, 2H), 0.98 (t, J=7.3 Hz, 3H)。 Example 176: 3 ′-{N ′-[5-fluoro-2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy -Biphenyl-3-carboxylic acid (Compound 276)

This compound was prepared as described in Scheme II. ¹ H NMR (300 MHz, acetone-d ₆ ) δ 8.19 (t, J = 1.5 Hz, 1H), 8.03 (m, 1H), 7.83 (dd, J = 7.8, 1.6 Hz, 1H), 7.77 (m, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.53 (dd, J = 8.3, 2.6 Hz, 1H), 7.47 (d, J = 8.8 Hz, 2H), 7.43 (d, J = 8.8 Hz, 2H), 7.13 (t, J = 7.8 Hz, 1H), 7.06-7.02 (m, 2H), 6.92 (dd, J = 8.8, 4.3 Hz, 1H), 2.69 (dd, J = 7.9, 7.3 Hz, 2H ), 1.71 (m, 2H), 0.98 (t, J = 7.3 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300 MHz, メタノール-d₄) δ 8.46 (s, 1H), 8.14 (m, 1H), 8.05 (s, 1H), 7.99 (d, J=7.6 Hz, 1H), 7.82 (dd, J=7.7, 1.4 Hz, 1H), 7.70 (d, J=7.6 Hz, 1H), 7.58 (m, 1H), 7.52 (t, J=7.6 Hz, 1H), 7.36 (m, 1H), 7.25 (s, 1H), 7.19 (m, 1H), 7.10 (t, J=7.7 Hz, 1H), 7.03 (dd, J=7.7, 1.4 Hz, 1H), 6.99 (m, 1H), 2.36 (s, 6H)。 Example 177: 3 ′-{N ′-[5-cyano-1- (3,4-dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ′ -Hydroxy-biphenyl-3-carboxylic acid (Compound 277)

This compound was prepared as described in Scheme II. ¹ H NMR (300 MHz, methanol-d ₄ ) δ 8.46 (s, 1H), 8.14 (m, 1H), 8.05 (s, 1H), 7.99 (d, J = 7.6 Hz, 1H), 7.82 (dd, J = 7.7, 1.4 Hz, 1H), 7.70 (d, J = 7.6 Hz, 1H), 7.58 (m, 1H), 7.52 (t, J = 7.6 Hz, 1H), 7.36 (m, 1H), 7.25 ( s, 1H), 7.19 (m, 1H), 7.10 (t, J = 7.7 Hz, 1H), 7.03 (dd, J = 7.7, 1.4 Hz, 1H), 6.99 (m, 1H), 2.36 (s, 6H ).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300 MHz, アセトン-d₆) δ 13.22 (s, 1H), 8.49 (s, 1H), 8.19 (t, J=1.6 Hz, 1H), 8.04 (ddd, J=7.7, 1.6, 1.2 Hz, 1H), 7.82-7.77 (m, 2H), 7.76 (d, J=8.0 Hz, 1H), 7.61 (t, J=7.7 Hz, 1H), 7.21 (dd, J=8.0, 1.8 Hz, 1H), 7.19-7.15 (m, 3H), 7.13 (t, J=7.7 Hz, 1H), 7.04 (dd, J=7.7, 1.6 Hz, 1H), 6.90 (d, J=1.8 Hz, 1H), 2.40 (s, 6H)。 Example 178: 3 ′-{N ′-[6-chloro-1- (3,5-dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ′ -Hydroxy-biphenyl-3-carboxylic acid (Compound 278)

This compound was prepared as described in Scheme II. ¹ H NMR (300 MHz, acetone-d ₆ ) δ 13.22 (s, 1H), 8.49 (s, 1H), 8.19 (t, J = 1.6 Hz, 1H), 8.04 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.82-7.77 (m, 2H), 7.76 (d, J = 8.0 Hz, 1H), 7.61 (t, J = 7.7 Hz, 1H), 7.21 (dd, J = 8.0, 1.8 Hz, 1H ), 7.19-7.15 (m, 3H), 7.13 (t, J = 7.7 Hz, 1H), 7.04 (dd, J = 7.7, 1.6 Hz, 1H), 6.90 (d, J = 1.8 Hz, 1H), 2.40 (s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (300 MHz, アセトン-d₆) δ 8.09 (dd, J=7.0, 2.4 Hz, 1H), 7.96 (d, J=7.9 Hz, 1H), 7.85 (dd, J=7.8, 1.6 Hz, 1H), 7.80 (ddd, J=8.5, 4.5, 2.4 Hz, 1H), 7.57-7.50 (m, 2H), 7.44-7.32 (m, 3H), 7.20 (m, 1H), 7.15 (t, J=7.8, 1H), 7.07 (dd, J=7.8, 1.6 Hz, 1H), 2.37 (d, J=1.9 Hz, 3H)。 Example 179: 4-Fluoro-3 '-{N'-[1- (3-fluoro-4-methyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3- Iridene] -hydrazino} -2′-hydroxy-biphenyl-3-carboxylic acid (Compound 279)

This compound was prepared as described in Scheme II. ¹ H NMR (300 MHz, acetone-d ₆ ) δ 8.09 (dd, J = 7.0, 2.4 Hz, 1H), 7.96 (d, J = 7.9 Hz, 1H), 7.85 (dd, J = 7.8, 1.6 Hz, 1H), 7.80 (ddd, J = 8.5, 4.5, 2.4 Hz, 1H), 7.57-7.50 (m, 2H), 7.44-7.32 (m, 3H), 7.20 (m, 1H), 7.15 (t, J = 7.8, 1H), 7.07 (dd, J = 7.8, 1.6 Hz, 1H), 2.37 (d, J = 1.9 Hz, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, CDCl₃) δ 7.75 (s, 1H), 7.45-7.41 (m, 2H), 7.39 (m, 1H), 7.09 (m, 1H), 3.25 (t, J = 7.3, 2H), 3.03 (t, J = 7.3, 2H), 1.81 (sext, J = 7.3, 2H), 1.63 (sext, J = 7.3, 2H), 1.12 (t, J = 7.3, 3H), 1.01 (t, J = 7.3, 3H)。 Example 180: 3 ′-{N ′-[1- (4-chloro-3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid (Compound 280)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, CDCl ₃ ) δ 7.75 (s, 1H), 7.45-7.41 (m, 2H), 7.39 (m, 1H), 7.09 (m, 1H), 3.25 (t, J = 7.3, 2H ), 3.03 (t, J = 7.3, 2H), 1.81 (sext, J = 7.3, 2H), 1.63 (sext, J = 7.3, 2H), 1.12 (t, J = 7.3, 3H), 1.01 (t, J = 7.3, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.35 (s, 1H), 8.01 (dd, J = 7.1, 2.4, 1H), 7.78 (ddd, J = 8.5, 4.5, 2.4, 1H), 7.66 (dd, J = 7.9, 1.6, 1H), 7.50 (d, J = 9.4, 1H), 7.41 (dd, J = 10.7, 8.5, 1H), 7.18 (s, 1H), 7.15 (s, 2H), 7.14 (t, J = 7.9, 1H), 7.07 (dd, J = 7.9, 1.6, 1H),6.83 (q, J = 0.7, 1H), 2.37 (s, 6H)。 Example 181: 3 ′-{N ′-[1- (3,5-dimethylphenyl) -4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -2'-hydroxybiphenyl-4-fluoro-3-carboxylic acid (Compound 281)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.35 (s, 1H), 8.01 (dd, J = 7.1, 2.4, 1H), 7.78 (ddd, J = 8.5, 4.5, 2.4, 1H), 7.66 ( dd, J = 7.9, 1.6, 1H), 7.50 (d, J = 9.4, 1H), 7.41 (dd, J = 10.7, 8.5, 1H), 7.18 (s, 1H), 7.15 (s, 2H), 7.14 (t, J = 7.9, 1H), 7.07 (dd, J = 7.9, 1.6, 1H), 6.83 (q, J = 0.7, 1H), 2.37 (s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.21 (s, 1H), 13.05 (s, 1H), 9.43 (s, 1H), 8.12 (t, J = 1.6, 1H), 7.95 (ddd, J = 7.7, 1.6, 1.2, 1H), 7.92 (d, J = 7.8, 1H), 7.80 (dd, J = 7.7, 1.6, 1.2, 1H), 7.78 (dd, J = 7.9, 1.6, 1H), 7.60 (t, J = 7.7, 1H), 7.54 (dq, J = 7.8, 0.8, 1H), 7.18 (d, J = 2.1, 1H), 7.14 (d, J = 8.2, 1H), 7.14 (t, J = 7.9, 1H), 7.06 (dd, J = 7.9, 1.6, 1H), 7.03 (dd, J = 8.2, 2.1, 1H), 6.98 (q, J = 0.6, 1H), 6.16 (s, 2H)。 Example 182: 3 '-{N'-[1-benzo [1,3] dioxo-5-yl-2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino}- 2'-hydroxybiphenyl-3-carboxylic acid (Compound 282)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.21 (s, 1H), 13.05 (s, 1H), 9.43 (s, 1H), 8.12 (t, J = 1.6, 1H), 7.95 (ddd, J = 7.7, 1.6, 1.2, 1H), 7.92 (d, J = 7.8, 1H), 7.80 (dd, J = 7.7, 1.6, 1.2, 1H), 7.78 (dd, J = 7.9, 1.6, 1H), 7.60 (t, J = 7.7, 1H), 7.54 (dq, J = 7.8, 0.8, 1H), 7.18 (d, J = 2.1, 1H), 7.14 (d, J = 8.2, 1H), 7.14 (t, J = 7.9, 1H), 7.06 (dd, J = 7.9, 1.6, 1H), 7.03 (dd, J = 8.2, 2.1, 1H), 6.98 (q, J = 0.6, 1H), 6.16 (s, 2H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.35 (s, 1H), 13.19 (s, 1H), 9.45 (s, 1H), 8.01 (dd, J = 7.2, 2.5, 1H), 7.91 (d, J = 7.9, 1H), 7.79 (ddd, J = 8.5, 4.6, 2.5, 1H), 7.77 (dd, J = 7.8, 1.6, 1H), 7.54 (dq, J = 7.9, 0.7 Hz, 1H), 7.42 (dd, J = 10.7, 8.5, 1H), 7.18 (d, J = 2.1, 1H), 7.14 (d, J = 8.2, 1H), 7.13 (t, J=7.8, 1H), 7.05 (dd, J = 7.8, 1.6, 1H), 7.03 (dd, J = 8.2, 2.1, 1H), 6.98 (q, J = 0.9, 1H), 6.16 (s, 2H)。 Example 183: 3 '-{N'-[1-benzo [1,3] dioxo-5-yl-2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino}- 2'-hydroxybiphenyl 2-fluoro-3-carboxylic acid (Compound 283)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.35 (s, 1H), 13.19 (s, 1H), 9.45 (s, 1H), 8.01 (dd, J = 7.2, 2.5, 1H), 7.91 (d , J = 7.9, 1H), 7.79 (ddd, J = 8.5, 4.6, 2.5, 1H), 7.77 (dd, J = 7.8, 1.6, 1H), 7.54 (dq, J = 7.9, 0.7 Hz, 1H), 7.42 (dd, J = 10.7, 8.5, 1H), 7.18 (d, J = 2.1, 1H), 7.14 (d, J = 8.2, 1H), 7.13 (t, J = 7.8, 1H), 7.05 (dd, J = 7.8, 1.6, 1H), 7.03 (dd, J = 8.2, 2.1, 1H), 6.98 (q, J = 0.9, 1H), 6.16 (s, 2H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.23 (s, 1H), 9.31 (s, 1H), 7.97 (d, J = 2.3, 1H), 7.92 (d, J = 7.9, 1H), 7.73 (dd, J = 7.8, 1.5, 1H), 7.69 (dd, J = 8.6, 2.3, 1H), 7.54 (dq, J = 7.9, 0.7, 1H), 7.17 (s, 1H), 7.16 (s, 2H), 7.10 (t, J = 7.8, 1H), 7.06 (d, J = 8.6, 1H), 7.02 (dd, J = 7.8, 1.5, 1H), 6.98 (d, J = 0.9, 1H), 2.37 (s, 6H)。 Example 184: 3 '-{N'-[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -2'- Hydroxybiphenyl-2-hydroxy-3-carboxylic acid (Compound 284)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.23 (s, 1H), 9.31 (s, 1H), 7.97 (d, J = 2.3, 1H), 7.92 (d, J = 7.9, 1H), 7.73 (dd, J = 7.8, 1.5, 1H), 7.69 (dd, J = 8.6, 2.3, 1H), 7.54 (dq, J = 7.9, 0.7, 1H), 7.17 (s, 1H), 7.16 (s, 2H ), 7.10 (t, J = 7.8, 1H), 7.06 (d, J = 8.6, 1H), 7.02 (dd, J = 7.8, 1.5, 1H), 6.98 (d, J = 0.9, 1H), 2.37 ( s, 6H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.20 (s, 1H), 13.05 (s, 1H), 9.45 (s, 1H), 8.15 (t, J = 1.7, 1H), 8.12 (t, J = 1.7, 1H), 8.10 (ddd, J = 7.8, 1.7, 1.2, 1H), 7.95 (m, 2H), 7.90 (m, 1H), 7.80 (t, J = 7.8, 1H), 7.82-7.78 (m, 2H), 7.61 (t, J = 7.8, 1H), 7.57 (dq, J = 7.9, 0.8, 1H), 7.15 (t, J = 7.8, 1H), 7.08 (m, 1H), 7.07 (dd, J = 7.8, 1.6, 1H), および3.90 (s, 3H)。 Example 185: 3 ′-{N ′-[1- (3-methoxycarbonylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -2′-hydroxy Biphenyl-3-carboxylic acid (Compound 285)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.20 (s, 1H), 13.05 (s, 1H), 9.45 (s, 1H), 8.15 (t, J = 1.7, 1H), 8.12 (t, J = 1.7, 1H), 8.10 (ddd, J = 7.8, 1.7, 1.2, 1H), 7.95 (m, 2H), 7.90 (m, 1H), 7.80 (t, J = 7.8, 1H), 7.82-7.78 ( m, 2H), 7.61 (t, J = 7.8, 1H), 7.57 (dq, J = 7.9, 0.8, 1H), 7.15 (t, J = 7.8, 1H), 7.08 (m, 1H), 7.07 (dd , J = 7.8, 1.6, 1H), and 3.90 (s, 3H).

この化合物は、反応式ＩＩに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.04 (s, 1H), 9.30 (s, 1H), 8.12 (t, J = 1.7, 1H), 8.12 (t, J = 1.7, 1H), 8.06 (ddd, J = 7.8, 1.7, 1.2, 1H), 7.94 (ddd, J = 7.8, 1.7, 1.2, 1H), 7.88 (m, 1H), 7.80 (ddd, J = 7.8, 1.7, 1.2, 1H), 7.77 (t, J = 7.8, 1H), 7.76 (dd, J = 7.6, 0.8, 1H), 7.74 (dd, J = 7.8, 1.6, 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.31 (td, J = 7.6, 1.3, 1H), 7.22 (td, J = 7.6, 0.8, 1H), 7.12 (t, J = 7.8, 1H), 7.01 (dd, J = 7.8, 1.6, 1H), 6.95 (d, J = 7.6, 1H), 4.11 (s, 1H), および3.90 (s, 3H)。 Example 186: 3 ′-{N ′-[1- (3-methoxycarbonylphenyl) -2-oxo-1,2-dihydroindole-3-ylidene] hydrazino} -2′-hydroxybiphenyl-3-carboxylic acid (Compound 286)

This compound was prepared as described in Scheme II. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.04 (s, 1H), 9.30 (s, 1H), 8.12 (t, J = 1.7, 1H), 8.12 (t, J = 1.7, 1H), 8.06 (ddd, J = 7.8, 1.7, 1.2, 1H), 7.94 (ddd, J = 7.8, 1.7, 1.2, 1H), 7.88 (m, 1H), 7.80 (ddd, J = 7.8, 1.7, 1.2, 1H) , 7.77 (t, J = 7.8, 1H), 7.76 (dd, J = 7.6, 0.8, 1H), 7.74 (dd, J = 7.8, 1.6, 1H), 7.60 (t, J = 7.8 Hz, 1H), 7.31 (td, J = 7.6, 1.3, 1H), 7.22 (td, J = 7.6, 0.8, 1H), 7.12 (t, J = 7.8, 1H), 7.01 (dd, J = 7.8, 1.6, 1H), 6.95 (d, J = 7.6, 1H), 4.11 (s, 1H), and 3.90 (s, 3H).

この化合物は、反応式Ｉに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.10 (s, 1H), 13.04 (s, 1H), 9.36 (s, 1H), 8.16 (dd, J = 5.1, 1.6 Hz, 1H), 8.12 (t, J = 1.6 Hz, 1H), 8.04 (dd, J = 7.4, 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.80 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.74 (dd, J = 7.8, 1.6 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.34 (d, J = 1.8 Hz, 1H), 7.30 (d, J = 8.1 Hz, 1H), 7.28 (dd, J = 8.1, 1.8 Hz, 1H), 7.21 (dd, J = 7.4, 5.1 Hz, 1H), 7.13 (t, J = 7.8 Hz, 1H), 7.03 (dd, J = 7.8, 1.6 Hz, 1H), 2.30 (s, 3H), 2.29 (s, 3H)。 Example 187: 3 ′-{N ′-[7-aza-1- (3,4-dimethylphenyl) -2-oxo-1,2-dihydroindole-3-ylidene] hydrazino} -2′-hydroxybiphenyl -3-carboxylic acid (compound 287)

This compound was prepared as described in Scheme I. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.10 (s, 1H), 13.04 (s, 1H), 9.36 (s, 1H), 8.16 (dd, J = 5.1, 1.6 Hz, 1H), 8.12 ( t, J = 1.6 Hz, 1H), 8.04 (dd, J = 7.4, 1.6 Hz, 1H), 7.94 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.80 (ddd, J = 7.7, 1.6, 1.2 Hz, 1H), 7.74 (dd, J = 7.8, 1.6 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.34 (d, J = 1.8 Hz, 1H), 7.30 (d, J = 8.1 Hz, 1H), 7.28 (dd, J = 8.1, 1.8 Hz, 1H), 7.21 (dd, J = 7.4, 5.1 Hz, 1H), 7.13 (t, J = 7.8 Hz, 1H), 7.03 (dd, J = 7.8, 1.6 Hz, 1H), 2.30 (s, 3H), 2.29 (s, 3H).

この化合物は、反応式Ｉに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.25 (s, 1H), 12.39 (s, 1H), 9.35 (s, 1H), 7.92 (d, J = 7.8 Hz, 1H), 7.75 (dd, J = 8.0, 1.5 Hz, 1H), 7.56-7.53 (m, 2H), 7.46-7.42 (m, 2H), 7.35 (m, 1H), 7.17 (s, 3H), 7.12 (t, J = 7.8 Hz, 1H), 7.02 (dd, J = 7.8, 1.6 Hz, 1H), 6.99 (q, J = 0.7 Hz, 1H), 2.37 (s, 6H), 1.52 (s, 6H)。 Example 188: 3 ′-{N ′-[1- (3,5-dimethylphenyl) -2-oxo-1,2-dihydroindole-6-trifluoromethyl-3-ylidene] hydrazino} -2′- Hydroxybiphenyl-3- (2-methyl-2-propionic acid) (Compound 288)

This compound was prepared as described in Scheme I. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.25 (s, 1H), 12.39 (s, 1H), 9.35 (s, 1H), 7.92 (d, J = 7.8 Hz, 1H), 7.75 (dd, J = 8.0, 1.5 Hz, 1H), 7.56-7.53 (m, 2H), 7.46-7.42 (m, 2H), 7.35 (m, 1H), 7.17 (s, 3H), 7.12 (t, J = 7.8 Hz , 1H), 7.02 (dd, J = 7.8, 1.6 Hz, 1H), 6.99 (q, J = 0.7 Hz, 1H), 2.37 (s, 6H), 1.52 (s, 6H).

この化合物は、反応式Ｉに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 8.14 (t, J = 1.3 Hz, 1H), 7.95 (d, J = 7.7 Hz, 1H), 7.81 (dt, J = 7.7, 1.3 Hz, 1H), 7.65 (d, J = 7.7 Hz, 1H), 7.61 (t, J = 7.7 Hz, 1H), 7.18 (dd, J = 7.7, 1.2 Hz, 1H), 7.13 (m, 1H), 3.22 (s, 6H)。 Example 189: 3 ′-{N ′-[1,3-N, N-dimethylbarbitur-5-ylidene] hydrazino} -2′-hydroxybiphenyl-3-carboxylic acid (Compound 289)

This compound was prepared as described in Scheme I. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 8.14 (t, J = 1.3 Hz, 1H), 7.95 (d, J = 7.7 Hz, 1H), 7.81 (dt, J = 7.7, 1.3 Hz, 1H) , 7.65 (d, J = 7.7 Hz, 1H), 7.61 (t, J = 7.7 Hz, 1H), 7.18 (dd, J = 7.7, 1.2 Hz, 1H), 7.13 (m, 1H), 3.22 (s, 6H).

この化合物は、反応式Ｉに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 14.24 (s, 1H), 13.06 (s, 1H), 9.49 (s, 1H), 8.36 (d, J = 7.9 Hz, 1H), 8.16-8.12 (m, 2H), 7.95 (d, J = 7.7 Hz, 1H), 7.88 (dd, J = 7.8, 1.0 Hz, 1H), 7.84-7.79 (m, 2H), 7.68 (d, J = 8.2 Hz, 2H), 7.61 (t, J = 7.7 Hz, 1H), 7.58 (d, J = 8.2 Hz, 2H), 7.55 (td, J = 7.7, 0.9 Hz, 1H), 7.15 (t, J = 7.8 Hz, 1H), 7.10 (dd, J = 7.8, 1.0 Hz, 1H), 5.28 (s, 2H)。 Example 190: 3 '-{N'-[1-N- (4-trifluoromethylbenzyl) -2,8-dioxo-1,2,7,8-tetrahydroisoquinoline-7-ylidene] hydrazino} -2 '-Hydroxybiphenyl-3-carboxylic acid (Compound 290)

This compound was prepared as described in Scheme I. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 14.24 (s, 1H), 13.06 (s, 1H), 9.49 (s, 1H), 8.36 (d, J = 7.9 Hz, 1H), 8.16-8.12 ( m, 2H), 7.95 (d, J = 7.7 Hz, 1H), 7.88 (dd, J = 7.8, 1.0 Hz, 1H), 7.84-7.79 (m, 2H), 7.68 (d, J = 8.2 Hz, 2H ), 7.61 (t, J = 7.7 Hz, 1H), 7.58 (d, J = 8.2 Hz, 2H), 7.55 (td, J = 7.7, 0.9 Hz, 1H), 7.15 (t, J = 7.8 Hz, 1H) ), 7.10 (dd, J = 7.8, 1.0 Hz, 1H), 5.28 (s, 2H).

この化合物は、反応式Ｉに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 14.28 (s, 1H), 13.06 (s, 1H), 9.49 (s, 1H), 8.34 (d, J = 8.0 Hz, 1H), 8.15-8.12 (m, 2H), 7.96 (dm, J = 7.8 Hz, 1H), 7.87 (dm, J = 7.8 Hz, 1H), 7.82-7.78 (m, 2H), 7.61 (t, J = 7.8 Hz, 1H), 7.54 (td, J = 7.7, 0.9 Hz, 1H), 7.25 (d, J = 8.2 Hz, 2H), 7.15 (t, J = 7.8 Hz, 1H), 7.10 (m, 1H), 7.12 (d, J = 8.2 Hz, 2H), 5.16 (s, 2H), 2.25 (s, 3H)。 Example 191: 3 ′-{N ′-[1-N- (4-methylbenzyl) -2,8-dioxo-1,2,7,8-tetrahydroisoquinoline-7-ylidene] hydrazino} -2′- Hydroxybiphenyl-3-carboxylic acid (Compound 291)

This compound was prepared as described in Scheme I. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 14.28 (s, 1H), 13.06 (s, 1H), 9.49 (s, 1H), 8.34 (d, J = 8.0 Hz, 1H), 8.15-8.12 ( m, 2H), 7.96 (dm, J = 7.8 Hz, 1H), 7.87 (dm, J = 7.8 Hz, 1H), 7.82-7.78 (m, 2H), 7.61 (t, J = 7.8 Hz, 1H), 7.54 (td, J = 7.7, 0.9 Hz, 1H), 7.25 (d, J = 8.2 Hz, 2H), 7.15 (t, J = 7.8 Hz, 1H), 7.10 (m, 1H), 7.12 (d, J = 8.2 Hz, 2H), 5.16 (s, 2H), 2.25 (s, 3H).

この化合物は、反応式Ｉに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 14.28 (s, 1H), 13.06 (s, 1H), 9.49 (s, 1H), 8.35 (d, J = 7.9 Hz, 1H), 8.16-8.12 (m, 2H), 7.95 (dd, J = 7.7, 1.2 Hz, 1H), 7.88 (d, J = 7.8 Hz, 1H), 7.82-7.78 (m, 2H), 7.61 (t, J = 7.7 Hz, 1H), 7.55 (td, J = 7.6, 0.8 Hz, 1H), 7.36 (d, J = 7.4 Hz, 2H), 7.32 (t, J = 7.4 Hz, 2H), 7.25 (t, J = 7.4 Hz, 1H), 7.15 (t, J = 7.8 Hz, 1H), 7.10 (dd, J = 7.8, 1.2 Hz, 1H), 5.21 (s, 2H)。 Example 192: 3 '-{N'-[1-N-benzyl-2,8-dioxo-1,2,7,8-tetrahydroisoquinoline-7-ylidene] hydrazino} -2'-hydroxybiphenyl-3- Carboxylic acid (Compound 292)

This compound was prepared as described in Scheme I. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 14.28 (s, 1H), 13.06 (s, 1H), 9.49 (s, 1H), 8.35 (d, J = 7.9 Hz, 1H), 8.16-8.12 ( m, 2H), 7.95 (dd, J = 7.7, 1.2 Hz, 1H), 7.88 (d, J = 7.8 Hz, 1H), 7.82-7.78 (m, 2H), 7.61 (t, J = 7.7 Hz, 1H ), 7.55 (td, J = 7.6, 0.8 Hz, 1H), 7.36 (d, J = 7.4 Hz, 2H), 7.32 (t, J = 7.4 Hz, 2H), 7.25 (t, J = 7.4 Hz, 1H) ), 7.15 (t, J = 7.8 Hz, 1H), 7.10 (dd, J = 7.8, 1.2 Hz, 1H), 5.21 (s, 2H).

この化合物は、反応式Ｉに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 14.11 (s, 1H), 13.05 (s, 1H), 9.41 (s, 1H), 8.42 (d, J = 8.0 Hz, 1H), 8.15-8.11 (m, 2H), 7.95 (dd, J = 7.7, 1.3 Hz, 1H), 7.93 (d, J = 8.2 Hz, 2H), 7.90 (dd, J = 7.8, 1.3 Hz, 1H), 7.85 (ddd, J = 8.0, 7.6, 1.3 Hz, 1H), 7.79 (dd, J = 7.7, 1.3 Hz, 1H), 7.67 (d, J = 8.2 Hz, 2H), 7.61 (t, J = 7.7 Hz, 1H), 7.58 (td, J = 7.6, 1.3 Hz, 1H), 7.16 (t, J = 7.8 Hz, 1H), 7.09 (dd, J = 7.8, 1.3 Hz, 1H)。 Example 193: 3 ′-{N ′-[1-N- (4-trifluoromethylphenyl) -2,8-dioxo-1,2,7,8-tetrahydroisoquinoline-7-ylidene] hydrazino} -2 '-Hydroxybiphenyl-3-carboxylic acid (Compound 293)

This compound was prepared as described in Scheme I. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 14.11 (s, 1H), 13.05 (s, 1H), 9.41 (s, 1H), 8.42 (d, J = 8.0 Hz, 1H), 8.15-8.11 ( m, 2H), 7.95 (dd, J = 7.7, 1.3 Hz, 1H), 7.93 (d, J = 8.2 Hz, 2H), 7.90 (dd, J = 7.8, 1.3 Hz, 1H), 7.85 (ddd, J = 8.0, 7.6, 1.3 Hz, 1H), 7.79 (dd, J = 7.7, 1.3 Hz, 1H), 7.67 (d, J = 8.2 Hz, 2H), 7.61 (t, J = 7.7 Hz, 1H), 7.58 (td, J = 7.6, 1.3 Hz, 1H), 7.16 (t, J = 7.8 Hz, 1H), 7.09 (dd, J = 7.8, 1.3 Hz, 1H).

この化合物は、反応式Ｉに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 14.11 (s, 1H), 13.05 (s, 1H), 9.41 (s, 1H), 8.42 (d, J = 7.9 Hz, 1H), 8.15-8.11 (m, 2H), 7.95 (dm, J = 7.7 Hz, 1H), 7.92-7.83 (m, 4H), 7.81-7.77 (m, 2H), 7.75 (d, J = 7.7 Hz, 1H), 7.61 (t, J = 7.7 Hz, 1H), 7.58 (td, J = 7.5, 1.0 Hz, 1H), 7.17 (t, J = 7.8 Hz, 1H), 7.09 (dd, J = 7.8, 1.2 Hz, 1H)。 Example 194: 3 ′-{N ′-[1-N- (3-trifluoromethylphenyl) -2,8-dioxo-1,2,7,8-tetrahydroisoquinoline-7-ylidene] hydrazino} -2 '-Hydroxybiphenyl-3-carboxylic acid (Compound 294)

This compound was prepared as described in Scheme I. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 14.11 (s, 1H), 13.05 (s, 1H), 9.41 (s, 1H), 8.42 (d, J = 7.9 Hz, 1H), 8.15-8.11 ( m, 2H), 7.95 (dm, J = 7.7 Hz, 1H), 7.92-7.83 (m, 4H), 7.81-7.77 (m, 2H), 7.75 (d, J = 7.7 Hz, 1H), 7.61 (t , J = 7.7 Hz, 1H), 7.58 (td, J = 7.5, 1.0 Hz, 1H), 7.17 (t, J = 7.8 Hz, 1H), 7.09 (dd, J = 7.8, 1.2 Hz, 1H).

この化合物は、反応式Ｉに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 14.18 (s, 1H), 13.06 (s, 1H), 9.38 (s, 1H), 8.38 (dd, J = 7.6, 0.9 Hz, 1H), 8.12-8.09 (m, 2H), 7.94 (dt, J = 7.7, 1.4 Hz, 1H), 7.88 (dd, J = 7.9, 1.3 Hz, 1H), 7.82 (td, J = 7.6, 0.9 Hz, 1H), 7.78 (dt, J = 7.7, 1.4 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.56 (td, J = 7.6, 0.9 Hz, 1H), 7.15 (t, J = 7.9 Hz, 1H), 7.10 (s, 1H), 7.08 (dd, J = 7.9, 1.3 Hz, 1H), 6.96 (s, 2H), 2.32 (s, 6H)。 Example 195: 3 ′-{N ′-[1-N- (3,5-dimethyl-phenyl) -2,8-dioxo-1,2,7,8-tetrahydroisoquinoline-7-ylidene] hydrazino}- 2'-hydroxybiphenyl-3-carboxylic acid (Compound 295)

This compound was prepared as described in Scheme I. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 14.18 (s, 1H), 13.06 (s, 1H), 9.38 (s, 1H), 8.38 (dd, J = 7.6, 0.9 Hz, 1H), 8.12- 8.09 (m, 2H), 7.94 (dt, J = 7.7, 1.4 Hz, 1H), 7.88 (dd, J = 7.9, 1.3 Hz, 1H), 7.82 (td, J = 7.6, 0.9 Hz, 1H), 7.78 (dt, J = 7.7, 1.4 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.56 (td, J = 7.6, 0.9 Hz, 1H), 7.15 (t, J = 7.9 Hz, 1H) , 7.10 (s, 1H), 7.08 (dd, J = 7.9, 1.3 Hz, 1H), 6.96 (s, 2H), 2.32 (s, 6H).

この化合物は、反応式Ｉに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 14.16 (s, 1H), 13.04 (s, 1H), 9.38 (s, 1H), 8.40 (dd, J = 7.7, 0.9 Hz, 1H), 8.14-8.10 (m, 2H), 7.94 (dt, J = 7.7, 1.4 Hz, 1H), 7.89 (dd, J = 7.8, 1.3 Hz, 1H), 7.83 (td, J = 7.7, 0.9 Hz, 1H), 7.78 (dt, J = 7.7, 1.4 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.57 (td, J = 7.7, 0.9 Hz, 1H), 7.53 (t, J = 7.5 Hz, 2H), 7.47 (t, J = 7.5 Hz, 1H), 7.38 (m, 2H), 7.15 (t, J = 7.8 Hz, 1H), 7.08 (dd, J = 7.8, 1.3 Hz, 1H)。 Example 196: 3 ′-{N ′-[1-N-phenyl-2,8-dioxo-1,2,7,8-tetrahydroisoquinoline-7-ylidene] hydrazino} -2′-hydroxybiphenyl-3- Carboxylic acid (Compound 296)

This compound was prepared as described in Scheme I. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 14.16 (s, 1H), 13.04 (s, 1H), 9.38 (s, 1H), 8.40 (dd, J = 7.7, 0.9 Hz, 1H), 8.14- 8.10 (m, 2H), 7.94 (dt, J = 7.7, 1.4 Hz, 1H), 7.89 (dd, J = 7.8, 1.3 Hz, 1H), 7.83 (td, J = 7.7, 0.9 Hz, 1H), 7.78 (dt, J = 7.7, 1.4 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.57 (td, J = 7.7, 0.9 Hz, 1H), 7.53 (t, J = 7.5 Hz, 2H) 7.47 (t, J = 7.5 Hz, 1H), 7.38 (m, 2H), 7.15 (t, J = 7.8 Hz, 1H), 7.08 (dd, J = 7.8, 1.3 Hz, 1H).

この化合物は、反応式Ｉに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 14.19 (s, 1H), 13.04 (s, 1H), 9.39 (s, 1H), 8.41 (dd, J = 7.6, 0.9 Hz, 1H), 8.14-8.10 (m, 2H), 7.94 (dt, J = 7.6, 1.4 Hz, 1H), 7.90 (dd, J = 7.8, 1.2 Hz, 1H), 7.85 (td, J = 7.6, 0.9 Hz, 1H), 7.78 (dt, J = 7.6, 1.4 Hz, 1H), 7.60 (t, J = 7.6 Hz, 1H), 7.57 (td, J = 7.6, 0.9 Hz, 1H), 7.27 (d, J = 7.4 Hz, 1H), 7.22 (t, J = 7.8 Hz, 1H), 7.18-7.12 (m, 2H), 7.08 (dd, J = 7.8, 1.2 Hz, 1H), 2.33 (s, 3H), 1.95 (s, 3H)。 Example 197: 3 ′-{N ′-[1-N- (3,4-dimethylphenyl) -2,8-dioxo-1,2,7,8-tetrahydroisoquinoline-7-ylidene] hydrazino} -2 '-Hydroxybiphenyl-3-carboxylic acid (Compound 297)

This compound was prepared as described in Scheme I. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 14.19 (s, 1H), 13.04 (s, 1H), 9.39 (s, 1H), 8.41 (dd, J = 7.6, 0.9 Hz, 1H), 8.14- 8.10 (m, 2H), 7.94 (dt, J = 7.6, 1.4 Hz, 1H), 7.90 (dd, J = 7.8, 1.2 Hz, 1H), 7.85 (td, J = 7.6, 0.9 Hz, 1H), 7.78 (dt, J = 7.6, 1.4 Hz, 1H), 7.60 (t, J = 7.6 Hz, 1H), 7.57 (td, J = 7.6, 0.9 Hz, 1H), 7.27 (d, J = 7.4 Hz, 1H) , 7.22 (t, J = 7.8 Hz, 1H), 7.18-7.12 (m, 2H), 7.08 (dd, J = 7.8, 1.2 Hz, 1H), 2.33 (s, 3H), 1.95 (s, 3H).

この化合物は、反応式Ｉに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.06 (s, 1H), 8.13 (m, 1H), 8.00 (dt, J = 7.8, 1.3 Hz, 1H), 7.94 (d, J = 7.9 Hz, 1H), 7.90 (m, 1H), 7.85 (m, 1H), 7.64 (t, J = 7.7 Hz, 1H), 7.56 (dq, J = 7.9, 0.7 Hz, 1H), 7.42 (t, J = 7.9 Hz, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.32 (d, J = 2.0 Hz, 1H), 7.30 (m, 1H), 7.26 (dd, J = 8.0, 2.0 Hz, 1H), 6.95 (q, J = 0.6 Hz, 1H), 2.31 (s, 3H), 2.29 (s, 3H)。 Example 198: 3 ′-{N ′-[1-N- (3,4-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -2 '-Fluorobiphenyl-3-carboxylic acid (Compound 298)

This compound was prepared as described in Scheme I. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.06 (s, 1H), 8.13 (m, 1H), 8.00 (dt, J = 7.8, 1.3 Hz, 1H), 7.94 (d, J = 7.9 Hz, 1H), 7.90 (m, 1H), 7.85 (m, 1H), 7.64 (t, J = 7.7 Hz, 1H), 7.56 (dq, J = 7.9, 0.7 Hz, 1H), 7.42 (t, J = 7.9 Hz, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.32 (d, J = 2.0 Hz, 1H), 7.30 (m, 1H), 7.26 (dd, J = 8.0, 2.0 Hz, 1H), 6.95 (q, J = 0.6 Hz, 1H), 2.31 (s, 3H), 2.29 (s, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.26 (s, 1H), 8.13 (d, J = 9.6 Hz, 1H), 8.03 (m, 1H), 7.96 (d, J = 7.9 Hz, 1H), 7.57 (dq, J = 7.9, 0.7 Hz, 1H), 7.48-7.44 (m, 2H), 7.40 (d, J = 8.1 Hz, 1H), 7.36 (d, J = 2.2 Hz, 1H), 7.29 (dd, J = 8.1, 2.2 Hz, 1H), 6.99 (m, 1H), 6.59 (d, J = 9.6 Hz, 1H), 2.33 (s, 3H), 2.32 (s, 3H)。 Example 199: 3- (3- {N '-[1-N- (3,4-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -2-hydroxyphenyl) -2 (Z) -propenoic acid (Compound 299)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.26 (s, 1H), 8.13 (d, J = 9.6 Hz, 1H), 8.03 (m, 1H), 7.96 (d, J = 7.9 Hz, 1H) , 7.57 (dq, J = 7.9, 0.7 Hz, 1H), 7.48-7.44 (m, 2H), 7.40 (d, J = 8.1 Hz, 1H), 7.36 (d, J = 2.2 Hz, 1H), 7.29 ( dd, J = 8.1, 2.2 Hz, 1H), 6.99 (m, 1H), 6.59 (d, J = 9.6 Hz, 1H), 2.33 (s, 3H), 2.32 (s, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.39 (s, 1H), 8.13 (d, J = 9.6 Hz, 1H), 7.90 (m, 1H), 7.55 (d, J = 9.5 Hz, 1H), 7.49-7.47 (m, 2H), 7.40 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 1.9 Hz, 1H), 7.29 (dd, J = 8.0, 1.9 Hz, 1H), 6.84 (s, 1H), 6.59 (d, J = 9.6 Hz, 1H), 2.33 (s, 3H), 2.32 (s, 3H)。 Example 200: 3- (3- {N '-[1-N- (3,4-dimethylphenyl) -2-oxo-4-fluoro-6-trifluoromethyl-1,2-dihydroindole-3- Iridene] hydrazino} -2-hydroxyphenyl) -2 (Z) -propenoic acid (Compound 300)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.39 (s, 1H), 8.13 (d, J = 9.6 Hz, 1H), 7.90 (m, 1H), 7.55 (d, J = 9.5 Hz, 1H) , 7.49-7.47 (m, 2H), 7.40 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 1.9 Hz, 1H), 7.29 (dd, J = 8.0, 1.9 Hz, 1H), 6.84 ( s, 1H), 6.59 (d, J = 9.6 Hz, 1H), 2.33 (s, 3H), 2.32 (s, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.29 (s, 1H), 8.06 (s, 1H), 7.70 (m, 1H), 7.50 (d, J = 9.6 Hz, 1H), 7.39 (d, J = 8.1 Hz, 1H), 7.32 (d, J = 2.1 Hz, 1H), 7.26 (dd, J = 8.1, 2.1 Hz, 1H), 7.17-7.14 (m, 2H), 6.80 (q, J = 0.7 Hz, 1H), 2.33 (s, 3H), 2.31 (s, 3H)。 Example 201: 5- (3- {N '-[1- (3,4-dimethylphenyl) -2-oxo-4-fluoro-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] Hydrazino} -2-hydroxybenzylidene) thiazolidine-2,4-dione (compound 301)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.29 (s, 1H), 8.06 (s, 1H), 7.70 (m, 1H), 7.50 (d, J = 9.6 Hz, 1H), 7.39 (d, J = 8.1 Hz, 1H), 7.32 (d, J = 2.1 Hz, 1H), 7.26 (dd, J = 8.1, 2.1 Hz, 1H), 7.17-7.14 (m, 2H), 6.80 (q, J = 0.7 Hz, 1H), 2.33 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.13 (s, 1H), 10.74 (s, 1H), 7.92 (d, J = 8.2 Hz, 1H), 7.85 (s, 1H), 7.77 (d, J = 8.6 Hz, 1H), 7.72 (d, J = 1.4 Hz, 1H), 7.54 (d, J = 8.2 Hz, 1H), 7.45 (dd, J = 8.6, 1.4 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 1.6 Hz, 1H), 7.27 (dd, J = 8.0, 1.6 Hz, 1H), 6.96 (m, 1H), 2.33 (s, 3H), 2.31 (s, 3H)。 Example 202: 2-chloro-3- (4- {N '-[1- (3,4-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] Hydrazino} -3-hydroxyphenyl) -2-propenoic acid (compound 302)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.13 (s, 1H), 10.74 (s, 1H), 7.92 (d, J = 8.2 Hz, 1H), 7.85 (s, 1H), 7.77 (d, J = 8.6 Hz, 1H), 7.72 (d, J = 1.4 Hz, 1H), 7.54 (d, J = 8.2 Hz, 1H), 7.45 (dd, J = 8.6, 1.4 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 1.6 Hz, 1H), 7.27 (dd, J = 8.0, 1.6 Hz, 1H), 6.96 (m, 1H), 2.33 (s, 3H), 2.31 ( s, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, アセトン-d₆) δ 13.32 (s, 1H), 10.78 (s, 1H), 9.52 (s, 1H), 7.95 (d, J = 7.9 Hz, 1H), 7.87 (d, J = 8.6 Hz, 1H), 7.61 (s, 1H), 7.52 (d, J = 7.9 Hz, 1H), 7.40 (d, J = 8.1 Hz, 1H), 7.37 (br s, 1H), 7.31 (br d, J = 8.1 Hz, 1H), 7.21 (s, 1H), 7.16 (d, J = 8.6 Hz, 1H), 7.10 (s, 1H), 2.61 (q, J = 7.3 Hz, 2H), 2.37 (s, 6H), 1.20 (t, J = 7.3 Hz, 3H)。 Example 203: 2-ethyl-3- (4- {N '-[1- (3,4-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] Hydrazino} -3-hydroxyphenyl) -2-propenoic acid (compound 303)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, acetone-d ₆ ) δ 13.32 (s, 1H), 10.78 (s, 1H), 9.52 (s, 1H), 7.95 (d, J = 7.9 Hz, 1H), 7.87 (d, J = 8.6 Hz, 1H), 7.61 (s, 1H), 7.52 (d, J = 7.9 Hz, 1H), 7.40 (d, J = 8.1 Hz, 1H), 7.37 (br s, 1H), 7.31 (br d, J = 8.1 Hz, 1H), 7.21 (s, 1H), 7.16 (d, J = 8.6 Hz, 1H), 7.10 (s, 1H), 2.61 (q, J = 7.3 Hz, 2H), 2.37 ( s, 6H), 1.20 (t, J = 7.3 Hz, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.17 (s, 1H), 13.13 (s, 1H), 11.43 (s, 1H), 11.35 (s, 1H), 10.64 (s, 1H), 10.58 (s, 1H), 7.92-7.88 (m, 3H), 7.72 (d, J = 8.3 Hz, 1H), 7.70 (d, J = 8.3 Hz, 1H), 7.53 (m, 2H), 7.50 (d, J = 8.3 Hz, 1H), 7.18 (s, 2H), 7.16 (s, 4H), 7.01 (d, J = 8.3 Hz, 1H), 6.98 (m, 2H), 6.95 (s, 1H), 6.59 (s, 1H), 6.35 (s, 1H), 3.10 (s, 3H), 2.93 (s, 3H), 2.37 (s, 12H)。 Example 204: 1-N-methyl-5- (4- {N '-[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3- Iridene] hydrazino} -3-hydroxybenzylidene) -1,3-diazolidine-2,4-dione (Compound 304)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.17 (s, 1H), 13.13 (s, 1H), 11.43 (s, 1H), 11.35 (s, 1H), 10.64 (s, 1H), 10.58 ( s, 1H), 7.92-7.88 (m, 3H), 7.72 (d, J = 8.3 Hz, 1H), 7.70 (d, J = 8.3 Hz, 1H), 7.53 (m, 2H), 7.50 (d, J = 8.3 Hz, 1H), 7.18 (s, 2H), 7.16 (s, 4H), 7.01 (d, J = 8.3 Hz, 1H), 6.98 (m, 2H), 6.95 (s, 1H), 6.59 (s , 1H), 6.35 (s, 1H), 3.10 (s, 3H), 2.93 (s, 3H), 2.37 (s, 12H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.14 (s, 1H), 11.21 (s, 1H), 10.57 (s, 1H), 10.48 (s, 1H), 7.91 (d, J = 7.9 Hz, 1H), 7.68 (d, J = 8.4 Hz, 1H), 7.51 (d, J = 7.9 Hz, 1H), 7.27 (d, J = 8.4 Hz, 1H), 7.15 (s, 1H), 7.14 (s, 2H), 7.05 (s, 1H), 6.96 (s, 1H), 6.32 (s, 1H), 2.35 (s, 6H)。 Example 205: 5- (4- {N '-[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -3 -Hydroxybenzylidene) -1,3-diazolidine-2,4-dione (Compound 305)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.14 (s, 1H), 11.21 (s, 1H), 10.57 (s, 1H), 10.48 (s, 1H), 7.91 (d, J = 7.9 Hz, 1H), 7.68 (d, J = 8.4 Hz, 1H), 7.51 (d, J = 7.9 Hz, 1H), 7.27 (d, J = 8.4 Hz, 1H), 7.15 (s, 1H), 7.14 (s, 2H), 7.05 (s, 1H), 6.96 (s, 1H), 6.32 (s, 1H), 2.35 (s, 6H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.56 (s, 1H), 13.12 (s, 1H), 10.69 (s, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.75 (d, J = 8.3 Hz, 1H), 7.54 (d, J = 8.0 Hz, 1H), 7.39 (d, J = 8.1 Hz, 1H), 7.36 (s, 1H), 7.33 (br s, 1H),7.29-7.25 (m, 2H), 6.95 (d, J = 36.7 Hz, 1H), 6.95 (m, 1H), 2.33 (s, 3H), 2.31 (s, 3H)。 Example 206: 2-Fluoro-3- (4- {N '-[1- (3,4-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] Hydrazino} -3-hydroxyphenyl) -2-propenoic acid (compound 306)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.56 (s, 1H), 13.12 (s, 1H), 10.69 (s, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.75 (d, J = 8.3 Hz, 1H), 7.54 (d, J = 8.0 Hz, 1H), 7.39 (d, J = 8.1 Hz, 1H), 7.36 (s, 1H), 7.33 (br s, 1H), 7.29-7.25 (m, 2H), 6.95 (d, J = 36.7 Hz, 1H), 6.95 (m, 1H), 2.33 (s, 3H), 2.31 (s, 3H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.10 (s, 1H), 10.43 (s, 1H), 7.86 (d, J = 7.9 Hz, 1H), 7.59 (d, J = 8.3 Hz, 1H), 7.51 (dq, J = 7.9, 0.7 Hz, 1H), 7.16 (s, 1H), 7.15 (s, 2H), 6.97 (q, J = 0.6 Hz, 1H), 6.83 (d, J = 1.6 Hz, 1H), 6.80 (dd, J = 8.3, 1.6 Hz, 1H), 3.88 (dd, J = 8.0, 4.6 Hz, 1H), 3.25 (s, 3H), 2.91 (dd, J = 14.2, 4.6 Hz, 1H), 2.80 (dd, J = 14.2, 8.0 Hz, 1H), 2.37 (s, 6H)。 Example 207: (±) -2-methoxy-3- (4- {N ′-[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole- 3-Ilidene] hydrazino} -3-hydroxyphenyl) propanoic acid (Compound 307)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.10 (s, 1H), 10.43 (s, 1H), 7.86 (d, J = 7.9 Hz, 1H), 7.59 (d, J = 8.3 Hz, 1H) , 7.51 (dq, J = 7.9, 0.7 Hz, 1H), 7.16 (s, 1H), 7.15 (s, 2H), 6.97 (q, J = 0.6 Hz, 1H), 6.83 (d, J = 1.6 Hz, 1H), 6.80 (dd, J = 8.3, 1.6 Hz, 1H), 3.88 (dd, J = 8.0, 4.6 Hz, 1H), 3.25 (s, 3H), 2.91 (dd, J = 14.2, 4.6 Hz, 1H ), 2.80 (dd, J = 14.2, 8.0 Hz, 1H), 2.37 (s, 6H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.18 (s, 1H), 12.08 (s, 1H), 9.26 (s, 1H), 7.89 (d, J = 7.9 Hz, 1H), 7.60 (dd, J = 7.8, 1.6 Hz, 1H), 7.52 (dq, J = 7.9, 0.7 Hz, 1H), 7.17 (s, 1H), 7.16 (s, 2H), 6.96 (m, 1H), 6.95 (t, J = 7.8 Hz, 1H), 6.88 (dd, J = 7.8, 1.6 Hz, 1H), 2.65 (t, J = 7.6 Hz, 2H), 2.37 (s, 6H), 2.25 (t, J = 7.6 Hz, 2H), 1.77 (qn, J = 7.6 Hz, 2H)。 Example 208: 4- (3- {N '-[1- (3,4-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -2 -Hydroxyphenyl) butanoic acid (Compound 308)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.18 (s, 1H), 12.08 (s, 1H), 9.26 (s, 1H), 7.89 (d, J = 7.9 Hz, 1H), 7.60 (dd, J = 7.8, 1.6 Hz, 1H), 7.52 (dq, J = 7.9, 0.7 Hz, 1H), 7.17 (s, 1H), 7.16 (s, 2H), 6.96 (m, 1H), 6.95 (t, J = 7.8 Hz, 1H), 6.88 (dd, J = 7.8, 1.6 Hz, 1H), 2.65 (t, J = 7.6 Hz, 2H), 2.37 (s, 6H), 2.25 (t, J = 7.6 Hz, 2H ), 1.77 (qn, J = 7.6 Hz, 2H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, DMSO-d₆) δ 13.0 (s, 1 H), 12.4 (s, 1 H), 10.1 (s, 1 H), 7.84 (d, J = 7.8 Hz, 1 H), 7.49 (d, J = 7.8 Hz, 1 H), 7.18 (s, 1 H), 7.15 (s, 2 H), 6.99 (dd, J = 8.8, 8.8 Hz, 1 H), 6.93 (s, 1 H), 6.68 (d, J = 8.3 Hz, 1 H), 6.30 (d, J = 7.8 Hz, 1 H), 4.28-4.26 (m, 2 H), 2.77-2.75 (m, 2 H), 2.37 (s, 6 H)。 Example 209: 3- (2- {N '-[1- (3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -3 -Hydroxyphenoxy) propanoic acid (Compound 309)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ 13.0 (s, 1 H), 12.4 (s, 1 H), 10.1 (s, 1 H), 7.84 (d, J = 7.8 Hz, 1 H), 7.49 (d, J = 7.8 Hz, 1 H), 7.18 (s, 1 H), 7.15 (s, 2 H), 6.99 (dd, J = 8.8, 8.8 Hz, 1 H), 6.93 (s, 1 H ), 6.68 (d, J = 8.3 Hz, 1 H), 6.30 (d, J = 7.8 Hz, 1 H), 4.28-4.26 (m, 2 H), 2.77-2.75 (m, 2 H), 2.37 ( s, 6 H).

この化合物は、反応式Ｖに記載する通り製造した。¹H NMR (500 MHz, CD₃OD) δ 7.84 (d, J = 7.8 Hz, 1 H), 7.65 (d, J = 8.4 Hz, 1 H), 7.44 (d, J = 7.8 Hz, 1 H), 7.18 (s, 1 H), 7.09 (s, 2 H), 6.99 (s, 1 H), 6.78 (d, J = 7.8 Hz, 1 H), 6.74 (s, 1 H), 2.60-2.57 (m, 2 H), 2.41 (s, 6 H), 2.29-2.26 (m, 2 H), 1.92-1.88 (m, 2 H)。 Example 210: 4- (4- {N '-[1- (3,4-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -3 -Hydroxyphenyl) butanoic acid (Compound 310)

This compound was prepared as described in Scheme V. ¹ H NMR (500 MHz, CD ₃ OD) δ 7.84 (d, J = 7.8 Hz, 1 H), 7.65 (d, J = 8.4 Hz, 1 H), 7.44 (d, J = 7.8 Hz, 1 H) , 7.18 (s, 1 H), 7.09 (s, 2 H), 6.99 (s, 1 H), 6.78 (d, J = 7.8 Hz, 1 H), 6.74 (s, 1 H), 2.60-2.57 ( m, 2 H), 2.41 (s, 6 H), 2.29-2.26 (m, 2 H), 1.92-1.88 (m, 2 H).

Claims (29)

Formula (III):

[Where:
R ¹ is selected from CO ₂ R ¹⁰ , CONR ¹⁰ R ¹¹ , or SO ₃ R ¹⁰ ;
R ² and ^{R 3} are each independently ^{hydrogen, OR 12, NR 12 R 13} , optionally substituted _C 1 -C ₄ alkyl, optionally substituted _C 1 -C ₄ haloalkyl, or (CH _{2), m} R or selected from ^14; or, R ² and R ³ form an olefin which is optionally substituted together;
R ⁴ is selected from hydrogen, F, Cl, Br, C ₁ -C ₄ alkyl, or C ₁ -C ₄ haloalkyl;
R ⁵ is selected from hydrogen, OR ¹⁰ , SR ¹⁰ , NHR ¹¹ , or CO ₂ H;
R ⁶ is selected from hydrogen, OR ¹² , NR ¹² R ¹³ , F, Cl, Br, C ₁ -C ₄ alkyl, C ₁ -C ₄ haloalkyl, or C ₁ -C ₄ heteroalkyl;
R ⁷ is (CH ₂ ) _m R ¹⁴ ;
R ⁸ and R ⁹ are each independently hydrogen, F, Cl, Br, CO ₂ R ¹⁰ , NO ₂ , CN, SO ₂ R ¹⁰ , (CH ₂ ) _m R ¹⁴ , C ₁ -C ₄ alkyl, or Selected from C ₁ -C ₄ haloalkyl;
R ¹⁰ is selected from hydrogen, optionally substituted C ₁ -C ₄ alkyl, or C ₁ -C ₄ haloalkyl;
R ¹¹ is selected from hydrogen, SO ₂ R ¹⁵ , C ₁ -C ₄ alkyl, or C ₁ -C ₄ haloalkyl;
R ¹² and R ¹³ are each independently selected from hydrogen, optionally substituted C ₁ -C ₄ alkyl, optionally substituted C ₁ -C ₄ haloalkyl, or (CH ₂ ) _m R ¹⁴ ;
R ¹⁴ is selected from optionally substituted aryl or optionally substituted heteroaryl;
R ¹⁵ is selected from hydrogen, C ₁ -C ₃ alkyl, or C ₁ -C ₃ haloalkyl;
m is 0, 1, or 2; and
n is 0 or 1]
Or a pharmaceutically acceptable salt thereof. 3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carbon acid;
2'-hydroxy-3 '-{N'-[2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3-carboxylic acid;
2'-hydroxy-3 '-{N'-[2-oxo-1- (4-ethyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3-carboxylic acid;
2'-hydroxy-3 '-{N'-[2-oxo-1- (4-trifluoromethoxy-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3-Fluoro-4-methoxy-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-4-carboxyl acid;
2'-hydroxy-3 '-{N'-[2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-4-carboxylic acid;
2'-hydroxy-3 '-{N'-[2-oxo-1- (4-ethyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-4-carboxylic acid;
3 '-{N'-[1- (4-tert-Butyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid;
2'-hydroxy-3 '-{N'-[2-oxo-1- (4-trifluoromethylphenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3-carboxylic acid ;
3 '-[N'-(1-benzyl-5-chloro-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2'-hydroxy-biphenyl-3-carboxylic acid;
3 '-[N'-(1-benzyl-5-methyl-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2'-hydroxy-biphenyl-3-carboxylic acid;
3 '-[N'-(1-benzyl-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2'-hydroxy-biphenyl-3-carboxylic acid;
2'-hydroxy-3 '-{N'-[2-oxo-1- (4-trifluoromethyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-4-carboxyl acid;
3 '-{N'-[1- (3,4-dichloro-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid;
2'-hydroxy-3 '-{N'-[1- (4-methyl-3-trifluoromethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl -3-carboxylic acid;
3 '-{N'-[1- (3-Fluoro-4-trifluoromethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[1- (3,5-bis-trifluoromethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
2'-hydroxy-3 '-{N'-[1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3-carboxylic acid;
3 '-{N'-[1- (2-Fluoro-4-trifluoromethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[1- (2-Fluoro-4-methyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -carboxylic acid;
3 '-{N'-[1- (4-Chloro-3-trifluoromethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 ′-{N ′-[1- (4-butyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2′-hydroxy-biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3-fluoro-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid;
2'-hydroxy-3 '-[N'-(2-oxo-1-m-tolyl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid;
3 '-{N'-[1- (4-fluoro-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid;
3 '-[N'-(1-benzyl-5-methoxy-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2'-hydroxy-biphenyl-3-carboxylic acid;
2'-hydroxy-3 '-{N'-[2-oxo-1- (3-trifluoromethyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3-carboxylic acid;
3 '-{N'-[5-Chloro-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -carboxylic acid;
3 '-{N'-[6-Chloro-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -carboxylic acid;
3 '-{N'-[5-Fluoro-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -carboxylic acid;
3 '-{N'-[5-methoxy-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -5-fluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[1- (4-Fluoro-3-trifluoromethyl-phenyl) -5-fluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,5-dichloro-phenyl) -5-fluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[1- (4-propyl-phenyl) -6-chloro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -carboxylic acid,
The compound according to claim 1, which is selected from: or a pharmaceutically acceptable salt thereof. (±) -2'-hydroxy-3 '-(N'-{2-oxo-1- [4- (2,2,2-trifluoro-1-hydroxy-ethyl) -phenyl] -1,2- Dihydro-indole-3-ylidene} -hydrazino) -biphenyl-3-carboxylic acid;
(±) -2'-hydroxy-3 '-(N'-{2-oxo-1- [4- (2,2,2-trifluoro-1-methoxy-ethyl) -phenyl] -1,2- Dihydro-indole-3-ylidene} -hydrazino) -biphenyl-3-carboxylic acid;
2'-hydroxy-3 '-(N'-{2-oxo-1- [4- (2,2,2-trifluoro-ethyl) -phenyl] -1,2-dihydro-indole-3-ylidene} -Hydrazino) -biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -4,5-dimethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -5-fluoro-4-methyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -5-fluoro-6-methyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid;
3 '-{N'-[4-Chloro-1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid;
3 '-{N'-[5-Chloro-2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -carboxylic acid;
2'-hydroxy-3 '-{N'-[1- (4-methylsulfanyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3-carboxylic acid ;
2'-hydroxy-3 '-{N'-[1- (4-methoxymethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3-carboxylic acid ;
(±) -2'-hydroxy-3 '-(N'-{2-oxo-1- [4- (2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl) -phenyl]- 1,2-dihydro-indole-3-ylidene} -hydrazino) -biphenyl-3-carboxylic acid;
3 '-{N'-[5-Fluoro-1- (4-methyl-3-trifluoromethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid;
2'-hydroxy-3 '-(N'-{2-oxo-1- [4- (2,2,2-trifluoro-1-methoxy-1-methyl-ethyl) -phenyl] -1,2- Dihydro-indole-3-ylidene} -hydrazino) -biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -6-fluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[6-Fluoro-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-5-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid;
3 '-{N'-[6-Fluoro-2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -carboxylic acid;
2'-hydroxy-3 '-{N'-[2-oxo-1- (4-propyl-phenyl) -5-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl -3-carboxylic acid;
3 '-{N'-[4,5-Difluoro-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
2'-hydroxy-3 '-[N'-(2-oxo-1-piperidin-4-yl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid;
3 '-{N'-[5-Fluoro-1- (2-fluoro-4-methyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid;
2'-hydroxy-3 '-[N'-(1-methyl-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid;
3 ′-[N ′-(1-cyclopentyl-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2′-hydroxy-biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -6-methyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
2'-hydroxy-3 '-[N'-(2-oxo-1-phenyl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid;
3 '-[N'-(6-Fluoro-2-oxo-1-phenyl-2,3-dihydro-1H-indol-3-yl) -hydrazino] -2'-hydroxy-biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -6-isopropyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -4-isopropyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -4-fluoro- 2'-hydroxy-biphenyl-3-carboxylic acid;
5'-Chloro-3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -4-fluoro-2'-hydroxy-biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -6-fluoro- 2'-hydroxy-biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -4,5-difluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] -hydrazino} -2'-hydroxy- 3-methyl-biphenyl-4-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-2,3-dihydro-1H-indol-3-yl] -hydrazino} -2- Fluoro-2'-hydroxy-biphenyl-4-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -4-fluoro-2-oxo-6-trifluoromethyl-2,3-dihydro-1H-indol-3-yl] -hydrazino } -4-Fluoro-2'-hydroxy-biphenyl-3-carboxylic acid;
5'-Chloro-3 '-{N'-[1- (3,4-dimethyl-phenyl) -4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene ] -Hydrazino} -4-fluoro-2'-hydroxy-biphenyl-3-carboxylic acid;
3-[(3'-Carboxy-2-hydroxy-biphenyl-3-yl) -hydrazono] -1- (3,5-dimethyl-phenyl) -2-oxo-2,3-dihydro-1H-indole-6 -Carboxylic acid methyl ester;
3-[(3'-carboxy-4'-fluoro-2-hydroxy-biphenyl-3-yl) -hydrazono] -1- (3,5-dimethyl-phenyl) -2-oxo-2,3-dihydro- 1H-indole-6-carboxylic acid methyl ester;
3-[(3'-Carboxy-4'-fluoro-2-hydroxy-biphenyl-3-yl) -hydrazono] -1- (3,4-dimethyl-phenyl) -2-oxo-2,3-dihydro- 1H-indole-6-carboxylic acid methyl ester;
3-[(3′-carboxy-5-chloro-4′-fluoro-2-hydroxy-biphenyl-3-yl) -hydrazono] -1- (3,5-dimethyl-phenyl) -2-oxo-2, 3-dihydro-1H-indole-6-carboxylic acid methyl ester;
3 '-{N'-[1- (2-Cyano-thiophen-3-yl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -carboxylic acid;
2'-hydroxy-3 '-[N'-(2-oxo-1-thiophen-3-yl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid;
3-[(3'-Carboxy-2-hydroxy-biphenyl-3-yl) -hydrazono] -1- (3,4-dimethyl-phenyl) -2-oxo-2,3-dihydro-1H-indole-6 -Carboxylic acid methyl ester;
3 '-{N'-[1- (4-Chloro-3-trifluoromethyl-phenyl) -6-cyano-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid;
5'-Chloro-3 '-{N'-[6-cyano-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -4-fluoro -2'-hydroxy-biphenyl-3-carboxylic acid;
3 '-{N'-[6-Cyano-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -4-fluoro-2'-hydroxy -Biphenyl-3-carboxylic acid;
(±) -1- (3,4-Dimethyl-phenyl) -3-{[2-hydroxy-3 '-(2,2,2-trifluoro-1-hydroxy-ethyl) -biphenyl-3-yl] -Hydrazono} -6-methanesulfonyl-1,3-dihydro-indol-2-one;
3 '-{N'-[6-Cyano-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -5-nitro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -6-methanesulfonyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy- Biphenyl-3-carboxylic acid;
3 '-{N'-[6-Cyano-1- (3,4-dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[1- (5-Cyano-pyridin-3-yl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -carboxylic acid;
3 '-[N'-(1-furan-3-yl-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2'-hydroxy-biphenyl-3-carboxylic acid;
3 '-[N'-(1-Benzo [1,3] dioxol-5-yl-2-oxo-1,2-dihydro-indole-3-ylidene) -hydrazino] -2'-hydroxy-biphenyl-3 -carboxylic acid;
2'-hydroxy-3 '-{N'-[1- (3-methyl-thiophen-2-yl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl-3 -carboxylic acid;
2'-hydroxy-3 '-[N'-(2-oxo-1-thiophen-2-yl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid;
2'-hydroxy-3 '-{N'-[1- (4-isopropyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl -3-carboxylic acid;
2'-hydroxy-3 '-{N'-[2-oxo-1- (4-propyl-phenyl) -6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl -3-carboxylic acid;
3 '-{N'-[1- (4-Ethyl-phenyl) -5,7-difluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -5,7-difluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid;
3 '-{N'-[5,7-Difluoro-2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[5,7-Difluoro-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -6-ethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -6-methoxy-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[5-Chloro-1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -6,7-dimethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid;
2- (3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 '-Hydroxy-biphenyl-4-yl) -2-methyl-propionic acid;
(-)-2- (3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene]- Hydrazino} -2'-hydroxy-biphenyl-4-yl) -propionic acid;
(+)-2- (3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene]- Hydrazino} -2'-hydroxy-biphenyl-4-yl) -propionic acid;
(±)-(3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-5'-methyl-biphenyl-4-yl) -propionic acid;
(±) -2- (3 ′-{N ′-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene]- Hydrazino} -5'-fluoro-2'-hydroxy-biphenyl-4-yl) -propionic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -5'-fluoro -2'-hydroxy-biphenyl-3-carboxylic acid;
5'-Chloro-3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -5'-methyl-biphenyl-3-carboxylic acid;
2'-hydroxy-3 '-{N'-[2-oxo-6-trifluoromethyl- (4-trifluoromethyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino}- Biphenyl-3-carboxylic acid;
3 '-{N'-[1- (4-Ethyl-3-methyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid;
3 '-{N'-[1- (4-Chloro-3-trifluoromethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,5-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -5'-fluoro -2'-hydroxy-biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -4,5 '-Difluoro-2'-hydroxy-biphenyl-3-carboxylicacid;
3 '-{N'-[1- (3,5-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -4,5 '-Difluoro-2'-hydroxy-biphenyl-3-carboxylicacid;
4,5'-difluoro-2'-hydroxy-3 '-{N'-[2-oxo-6-trifluoromethyl 1- (4-trifluoromethyl-phenyl) -1,2-dihydro-indole-3 -Ylidene] -hydrazino} -biphenyl-3-carboxylic acid;
3 '-{N'-[1- (4-Fluoro-3,5-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid;
2'-hydroxy-3 '-{N'-[1- (4-methoxy-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl -3-carboxylic acid;
3 '-{N'-[1- (4-Fluoro-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[1- (3,5-dimethoxy-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethoxy-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,5-Difluoro-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid;
5'-fluoro-3 '-{N'-[1- (4-fluoro-3,5-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene ] -Hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid;
4,5'-difluoro-3 '-{N'-[1- (4-fluoro-3,5-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3 -Ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid;
2'-hydroxy-3 '-{N'-[1- (4-methoxy-3,5-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene ] -Hydrazino} -biphenyl-3-carboxylic acid;
2'-hydroxy-3 '-{N'-[1- (4-hydroxy-3,5-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene ] -Hydrazino} -biphenyl-3-carboxylic acid;
3 '-{N'-[1- (4-cyclohexyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid;
2'-hydroxy-3 '-[N'-(2-oxo-1-pyridin-2-yl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid;
2'-hydroxy-3 '-[N'-(2-oxo-1-pyridin-3-yl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid;
3 '-{N'-[1- (4-Ethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[1- (4-Ethyl-phenyl) -4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid;
3-[(3'-Carboxy-2-hydroxy-biphenyl-3-yl) -hydrazono] -1- (3,5-dimethyl-phenyl) -2-oxo-2,3-dihydro-1-H-indole -5-carboxylic acid methyl ester;
3 '-{N'-[1- (3-Chloro-4-methyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' -Hydroxy-biphenyl-3-carboxylic acid;
2'-hydroxy-3 '-(N'-{2-oxo-1- [4- (4,4,4-trifluoro-butyl) -phenyl] -1,2-dihydro-indole-3-ylidene} -Hydrazino) -biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,5-Dimethyl-phenyl) -4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid;
3 '-{N'-[1- (4-tert-butyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-4-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-bromo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[1- (3,4-dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -3-fluoro- 2'-hydroxy-biphenyl-4-carboxylic acid;
3 '-{N'-[1- (3,5-bis-trifluoromethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2'-hydroxy-biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,4-dichloro-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,5-dichloro-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid;
2'-hydroxy-3 '-[N'-(2-oxo-7-phenyl-1,2-dihydro-indole-3-ylidene) -hydrazino] -biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethoxy-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6- (1,1,2,2-tetrafluoro-ethoxy) -1,2-dihydro-indole-3 -Ylidene] -hydrazino} -2'-hydroxy-biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -5-methyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[1- (4-Isopropyl-phenyl) -5-methyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -carboxylic acid;
3 '-{N'-[1- (3,4-Dimethyl-phenyl) -6-phenyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[1- (3-trifluoromethyl-phenyl) -6-trifluoromethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid;
3 '-{N'-[1- (4-trifluoromethoxy-phenyl) -5-trifluoromethoxy-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,5-Dimethyl-phenyl) -6-trifluoromethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3-trifluoromethyl-phenyl) -4,6-dimethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3-trifluoromethyl-phenyl) -5,6-dimethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -Biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,5-Dimethyl-phenyl) -6-trifluoromethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -5'-chloro-4-fluoro-biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,5-Dimethyl-phenyl) -6-trifluoromethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy -4-fluoro-biphenyl-3-carboxylic acid;
3 '-{N'-[6-Chloro-1- (3,4-dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[5-Fluoro-2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 -carboxylic acid;
3 '-{N'-[5-Cyano-1- (3,4-dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
3 '-{N'-[6-Chloro-1- (3,5-dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl -3-carboxylic acid;
4-Fluoro-3 '-{N'-[1- (3-fluoro-4-methyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino } -2'-hydroxy-biphenyl-3-carboxylic acid,
The compound according to claim 1, which is selected from: or a pharmaceutically acceptable salt thereof. 3 '-{N'-[1- (4-Chloro-3,5-dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -2'- Hydroxy-biphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,5-Dimethylphenyl) -4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -2'- Hydroxybiphenyl-4-fluoro-3-carboxylic acid;
3 '-{N'-[1-Benzo [1,3] dioxo-5-yl-2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -2'-hydroxy Biphenyl-3-carboxylic acid;
3 '-{N'-[1-Benzo [1,3] dioxo-5-yl-2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -2'-hydroxy Biphenyl-2-fluoro-3-carboxylic acid;
3 '-{N'-[1- (3,5-Dimethylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -2'-hydroxybiphenyl-2 -Hydroxy-3-carboxylic acid;
3 '-{N'-[1- (3-methoxycarbonylphenyl) -2-oxo-6-trifluoromethyl-1,2-dihydroindole-3-ylidene] hydrazino} -2'-hydroxybiphenyl-3- carboxylic acid;
3 '-{N'-[1- (3-methoxycarbonylphenyl) -2-oxo-1,2-dihydroindole-3-ylidene] hydrazino} -2'-hydroxybiphenyl-3-carboxylic acid;
3 '-{N'-[1- (3,5-Dimethylphenyl) -2-oxo-1,2-dihydroindole-6-trifluoromethyl-3-ylidene] hydrazino} -2'-hydroxybiphenyl-3- (2-methyl-2-propionic acid),
The compound according to claim 1, which is selected from: or a pharmaceutically acceptable salt thereof. R ¹ is CO ₂ R ¹⁰ ;
R ⁴ is hydrogen;
R ⁵ is OR ¹⁰ ;
R ⁶ is hydrogen;
R ⁷ is phenyl substituted with alkyl;
R ⁸ is hydrogen, F, Cl, or Br;
R ⁹ is F, Cl, Br, or C ₁ -C ₄ haloalkyl;
R ¹⁰ is hydrogen; and
n is 0,
The compound of claim 1.   3 '-{N'-[6-Chloro-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 The compound according to claim 1, which is selected from -carboxylic acids or pharmaceutically acceptable salts thereof.   3 '-{N'-[1- (4-propyl-phenyl) -6-chloro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 The compound according to claim 1, which is selected from -carboxylic acids or pharmaceutically acceptable salts thereof.   3 '-{N'-[1- (3,4-Dimethyl-phenyl) -4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2. A compound according to claim 1 selected from 2'-hydroxy-biphenyl-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.   3 '-{N'-[1- (3,4-Dimethyl-phenyl) -6-fluoro-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl 2. A compound according to claim 1 selected from -3-carboxylic acids or pharmaceutically acceptable salts thereof.   3 '-{N'-[6-Fluoro-1- (4-isopropyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 The compound according to claim 1, which is selected from -carboxylic acids or pharmaceutically acceptable salts thereof.   3 '-{N'-[6-Fluoro-2-oxo-1- (4-propyl-phenyl) -1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl-3 The compound according to claim 1, which is selected from -carboxylic acids or pharmaceutically acceptable salts thereof.   2'-hydroxy-3 '-{N'-[1- (4-isopropyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl 2. A compound according to claim 1 selected from -3-carboxylic acids or pharmaceutically acceptable salts thereof.   2'-hydroxy-3 '-{N'-[2-oxo-1- (4-propyl-phenyl) -6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -biphenyl 2. A compound according to claim 1 selected from -3-carboxylic acids or pharmaceutically acceptable salts thereof.   3 '-{N'-[1- (3,4-Dimethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy The compound according to claim 1, which is selected from -biphenyl-3-carboxylic acid or a pharmaceutically acceptable salt thereof.   3 '-{N'-[1- (4-Ethyl-phenyl) -2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl 2. A compound according to claim 1 selected from -3-carboxylic acids or pharmaceutically acceptable salts thereof.   3 '-{N'-[1- (4-Ethyl-phenyl) -4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino} -2 ' 2. A compound according to claim 1 selected from -hydroxy-biphenyl-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.   3 '-{N'-[1- (3,5-Dimethyl-phenyl) -4-fluoro-2-oxo-6-trifluoromethyl-1,2-dihydro-indole-3-ylidene] -hydrazino}- 2. A compound according to claim 1 selected from 2'-hydroxy-biphenyl-3-carboxylic acid, or a pharmaceutically acceptable salt thereof.   3 '-{N'-[1- (3,5-Dimethyl-phenyl) -6-trifluoromethyl-2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy The compound according to claim 1, which is selected from -biphenyl-3-carboxylic acid or a pharmaceutically acceptable salt thereof.   3 '-{N'-[6-Chloro-1- (3,4-dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl 2. A compound according to claim 1 selected from -3-carboxylic acids or pharmaceutically acceptable salts thereof.   3 '-{N'-[6-Chloro-1- (3,5-dimethyl-phenyl) -2-oxo-1,2-dihydro-indole-3-ylidene] -hydrazino} -2'-hydroxy-biphenyl 2. A compound according to claim 1 selected from -3-carboxylic acids or pharmaceutically acceptable salts thereof. R ¹ is selected from CO ₂ R ¹⁰ ;
And R ² and ^{R 3} are each independently, selected from C ₁ -C ₄ alkyl;
R ⁴ is selected from hydrogen, F, Cl, Br, or C ₁ -C ₄ alkyl;
R ⁵ is OR ¹⁰ ;
R ⁶ is selected from OR ¹² , F, Cl, Br, or C ₁ -C ₄ alkyl;
R ⁷ is (CH ₂ ) _m R ¹⁴ ;
R ⁸ and R ⁹ are each independently selected from hydrogen, F, Cl, Br, CO ₂ R ¹⁰ , NO ₂ , CN, SO ₂ R ¹⁰ , C ₁ -C ₄ alkyl, or C ₁ -C ₄ haloalkyl. That;
R ¹⁰ is selected from hydrogen or methyl;
R ¹² is hydrogen;
R ¹⁴ is selected from optionally substituted aryl;
m is 1, and
n is 0,
The compound of claim 1. The compound of claim 21, wherein R ¹⁴ is phenyl.   23. A compound according to any one of claims 1 to 22 which is a selective thrombopoietin (TPO) modifier.   24. The compound of claim 23, which is a thrombopoietin (TPO) mimetic.   24. The compound of claim 23, which is a selective thrombopoietin (TPO) receptor agonist.   24. The compound of claim 23, which is a selective thrombopoietin (TPO) receptor partial agonist.   24. The compound of claim 23, which is a selective thrombopoietin (TPO) receptor antagonist.   23. A compound according to any one of claims 1-22, which is a selective thrombopoietin (TPO) receptor binding compound. formula:

A compound represented by